Displaying publications 1 - 20 of 454 in total

Abstract:
Sort:
  1. Fulltext Brazilian red propolis: phytochemical screening, antioxidant activity and effect against cancer cells
    de Mendonça IC, Porto IC, do Nascimento TG, de Souza NS, Oliveira JM, Arruda RE, et al.
    BMC Complement Altern Med, 2015 Oct 14;15:357.
    PMID: 26467757 DOI: 10.1186/s12906-015-0888-9
    BACKGROUND: The implementation of new public healthcare models that stimulate the use of natural products from traditional medicine, as a so-called integrated medicine, refers to an approach that use best of both conventional medicine and traditional medicine. Propolis is a widely used natural product by different ancient cultures and known to exhibit biological activities beneficial for health. The large number of studies conducted with propolis had shown that its chemical composition differs as a function of the climate, plant diversity and bee species and plays an important role on its therapeutic properties. The aim of this study was to analyse the phytochemical profile of the ethanolic extract of red propolis (EEP) and its fractionation, antioxidant action of EEP and its fractions hexane, cloroform and ethyl acetate and cytotoxic activity of EEP on human tumour cell lines SF-295 (glioblastoma), OVCAR-8 (ovary) and HCT-116 (colon).

    METHODS: EEP was obtained by maceration with absolute ethanol, then it was concentrated in rotaevaporator up to complete evaporation of the solvent. The crude extract was fractionated with hexane, ethyl acetate, chloroform and methanol and they were subjected to phytochemical screening and total phenolic compounds. Antioxidant activity of EEP and fractions was done by means of the 2,2-diphenyl-1-picryhydrazyl (DPPH) method. Biomarkers of red propolis were identified by LC-Orbitrap-FTMS. To assess cytotoxic activity of the extract, cells were exposed to EEP over 72 h. Cell viability was assessed by means of MTT assay. The percentage of cell growth inhibition (IC50) was analysed by means of non-linear regression, and the absorbance values of the various investigated concentrations were subjected to one-factor analysis of variance (ANOVA) followed by Tukey's or Tamhane's tests (α = 0.05).

    RESULTS: The results obtained using phytochemical screening and LC-Orbitrap-FTMS indicated the presence of phlobaphene tannins, catechins, chalcones, aurones, flavonones, flavonols, xanthones, pentacyclic triterpenoids and guttiferones in Brazilian red propolis. EEP and its hexane, chloroform and ethyl acetate fractions obtained by liquid-liquid partitioning exhibited satisfactory antioxidant percentages. EEP (IC50 

    Matched MeSH terms: Antineoplastic Agents/pharmacology
  2. Fulltext A Bottom-Up Synthesis Approach to Silver Nanoparticles Induces Anti-Proliferative and Apoptotic Activities Against MCF-7, MCF-7/TAMR-1 and MCF-10A Human Breast Cell Lines
    Zulkifli NI, Muhamad M, Mohamad Zain NN, Tan WN, Yahaya N, Bustami Y, et al.
    Molecules, 2020 Sep 22;25(18).
    PMID: 32971740 DOI: 10.3390/molecules25184332
    A bottom-up approach for synthesizing silver nanoparticles (AgNPs-GA) phytomediated by Garcinia atroviridis leaf extract is described. Under optimized conditions, the AgNPs-GA were synthesized at a concentration of 0.1 M silver salt and 10% (w/v) leaf extract, 1:4 mixing ratio of reactants, pH 3, temperature 32 °C and 72 h reaction time. The AgNPs-GA were characterized by various analytical techniques and their size was determined to be 5-30 nm. FTIR spectroscopy indicates the role of phenolic functional groups in the reduction of silver ions into AgNPs-GA and in supporting their subsequent stability. The UV-Visible spectrum showed an absorption peak at 450 nm which reflects the surface plasmon resonance (SPR) of AgNPs-GA and further supports the stability of these biosynthesized nanoparticles. SEM, TEM and XRD diffractogram analyses indicate that AgNPs-GA were spherical and face-centered-cubic in shape. This study also describes the efficacy of biosynthesized AgNPs-GA as anti-proliferative agent against human breast cancer cell lines, MCF-7 and MCF-7/TAMR-1. Our findings indicate that AgNPs-GA possess significant anti-proliferative effects against both the MCF-7 and MCF-7/TAMR-1 cell lines, with inhibitory concentration at 50% (IC50 values) of 2.0 and 34.0 µg/mL, respectively, after 72 h of treatment. An induction of apoptosis was evidenced by flow cytometry using Annexin V-FITC and propidium iodide staining. Therefore, AgNPs-GA exhibited its anti-proliferative activity via apoptosis on MCF-7 and MCF-7/TAMR-1 breast cancer cells in vitro. Taken together, the leaf extract from Garcinia atroviridis was found to be highly capable of producing AgNPs-GA with favourable physicochemical and biological properties.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  3. Fulltext Vitamin E (α-Tocopherol) Exhibits Antitumour Activity on Oral Squamous Carcinoma Cells ORL-48
    Zulkapli R, Abdul Razak F, Zain RB
    Integr Cancer Ther, 2017 09;16(3):414-425.
    PMID: 28818030 DOI: 10.1177/1534735416675950
    Cancers involving the oral cavity, head, and neck regions are often treated with cisplatin. In cancer therapy, the main target is to eliminate unwanted cancerous cells. However, reports on the nonselective nature of this drug have raised few concerns. Incorrect nutritional habits and lifestyle practices have been directly linked to cancer incidence. Nutrients with antioxidant activity inhibit cancer cells development, destroying them through oxidative stress and apoptosis. α-tocopherol, the potent antioxidant form of vitamin E is a known scavenger of free radicals. In vitro study exhibited effective antitumor activity of α-tocopherol on ORL-48 at 2.5 ± 0.42 µg/mL. Cisplatin exhibited stronger activity at 1.0 ± 0.15 µg/mL, but unlike α-tocopherol it exhibited cytotoxicity on normal human epidermal keratinocytes at very low concentration (<0.1 µg/mL). Despite the lower potency of α-tocopherol, signs of apoptosis such as the shrinkage of cells and appearance of apoptotic bodies were observed much earlier than cisplatin in time lapse microscopy. No apoptotic vesicles were formed with cisplatin, instead an increased population of cells in the holoclone form which may suggest different induction mechanisms between both agents. High accumulation of cells in the G0/G1 phase were observed through TUNEL and annexin V-biotin assays, while the exhibition of ultrastructural changes of the cellular structures verified the apoptotic mode of cell death by both agents. Both cisplatin and α-tocopherol displayed cell cycle arrest at the Sub G0 phase. α-tocopherol thus, showed potential as an antitumour agent for the treatment of oral cancer and merits further research.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  4. Annona muricata leaves induce G₁ cell cycle arrest and apoptosis through mitochondria-mediated pathway in human HCT-116 and HT-29 colon cancer cells
    Zorofchian Moghadamtousi S, Karimian H, Rouhollahi E, Paydar M, Fadaeinasab M, Abdul Kadir H
    J Ethnopharmacol, 2014 Oct 28;156:277-89.
    PMID: 25195082 DOI: 10.1016/j.jep.2014.08.011
    ETHNOPHARMACOLOGICAL RELEVANCE: Annona muricata known as "the cancer killer" has been widely used in the traditional medicine for the treatment of cancer and tumors. The purpose of this study is to investigate the anticancer properties of ethyl acetate extract of Annona muricata leaves (EEAM) on HT-29 and HCT-116 colon cancer cells and the underlying mechanisms.
    MATERIALS AND METHODS: The effect of EEAM on the cell proliferation of HT-29 and HCT-116 cells was analyzed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) assay. High content screening system (HCS) was applied to investigate the cell membrane permeability, mitochondrial membrane potential (MMP), nuclear condensation and cytochrome c translocation from mitochondria to cytosol. Reactive oxygen species (ROS) formation, lactate dehydrogenase (LDH) release and activation of caspase-3/7, -8 and -9 were measured while treatment. Flow cytometric analysis was used to determine the cell cycle distribution and phosphatidylserine externalization. The protein expression of Bax and Bcl-2 was determined using immunofluorescence analysis. In addition, the potential of EEAM to suppress the migration and invasion of colon cancer cells was also examined.
    RESULTS: EEAM exerted significant cytotoxic effects on HCT-116 and HT-29 cells as determined by MTT and LDH assays. After 24 h treatment, EEAM exhibited the IC₅₀ value of 11.43 ± 1.87 µg/ml and 8.98 ± 1.24 µg/ml against HT-29 and HCT-116 cells, respectively. Flow cytometric analysis demonstrated the cell cycle arrest at G1 phase and phosphatidylserine externalization confirming the induction of apoptosis. EEAM treatment caused excessive accumulation of ROS followed by disruption of MMP, cytochrome c leakage and activation of the initiator and executioner caspases in both colon cancer cells. Immunofluorescence analysis depicted the up-regulation of Bax and down-regulation of Bcl-2 proteins while treated with EEAM. Furthermore, EEAM conspicuously blocked the migration and invasion of HT-29 and HCT-116 cells.
    CONCLUSIONS: These findings provide a scientific basis for the use of A. muricata leaves in the treatment of cancer, although further in vivo studies are still required.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  5. Curcumin Modulates Hepatocellular Carcinoma by Reducing UNC119 Expression
    Zhao Z, Malhotra A, Seng WY
    J Environ Pathol Toxicol Oncol, 2019;38(3):195-203.
    PMID: 31679307 DOI: 10.1615/JEnvironPatholToxicolOncol.2019029549
    UNCI 19 expression has been reported to be significantly higher in hepatic cancer cells (HCC). However, the clinical significance of modulating UNC119 expression in HCC is not well understood. The study described here aimed to explore the potential of curcumin in modulation of UNC119 expression in HCC by assessment with quantitative real-time PCR, western blot, and immune-histochemical analyses in HCC cell lines and tissues. The biological functions of UNC119 in the proliferation, growth, and cycle of tumor cells were analyzed both in vitro and in vivo. UNC119 expression was upregulated in HCC cell lines and tissues as indicated by comparison with normal liver cells and tissues. Cellular function assays showed that higher levels of UNC119 not only promoted proliferation but also enhanced HCC cell migration and invasion. UNC119 promoted progression of the cell cycle and significantly promoted HCC cell growth through the Wnt/β-catenin signal pathway, and enhanced tumor migration and invasion by the TGF-β/EMT pathway. Curcumin efficiently inhibited HCC cell proliferation by blocking the Wnt/β-catenin pathway and inhabited migration and invasion by blocking the TGF-p/EMT signal pathway. Curcumin not only was beneficial for tumor remission but also contributed to the long-term survival of HCC-bearing mice. UNC119 was significantly upregulated and promoted cell growth in hepatic cancer cells and tissues by the Wnt/β-catenin signal pathway and migration by TGF-β/EMT signal pathway. Curcumin treatment inhibited cell proliferation, growth, migration, and invasion by inhibition of those pathways.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  6. Miltefosine suppression of Pten null T-ALL leukemia via β-catenin degradation through inhibition of pT308-Akt and TGFβ1/Smad3
    Zhang Y, Lee S, Xu W
    Biochem Biophys Res Commun, 2020 04 16;524(4):1018-1024.
    PMID: 32063363 DOI: 10.1016/j.bbrc.2020.02.021
    Pten deletion in the hematopoietic stem cells (HSC) causes a myeloproliferative disorder, which may subsequently develop into a T-cell acute lymphoblastic leukemia (T-ALL). β-catenin expression was dramatically increased in the c-KitmidCD3+Lin- leukemia stem cells (LSC) and was critical for T-ALL development. Therefore, the inactivation of β-catenin in LSC may have a potential to eliminate the LSC. In this study, we investigated the mechanism of enhancement of the β-catenin expression and subsequently used a drug to inactivate β-catenin expression in T-ALL. Western blot (WB) analysis revealed an increased level of β-catenin in the leukemic cells, but not in the pre-leukemic cells. Furthermore, the WB analysis of the thymic cells from different stages of leukemia development showed that increased expression of β-catenin was not via the pS9-GSK3β signaling, but was dependent on the pT308-Akt activation. Miltefosine (Hexadecylphosphocholine) is the first oral anti-Leishmania drug, which is a phospholipid agent and has been shown to inhibit the PI3K/Akt activity. Treatment of the PtenΔ/Δ leukemic mice with Miltefosine for different durations demonstrated that the pT308-Akt and the β-catenin expressions were inhibited in the leukemia blast cells. Miltefosine treatment also suppressed the TGFβ1/Smad3 signaling pathway. Analysis of TGFβ1 in the sorted subpopulations of the blast cells showed that TGFβ1 was secreted by the CD3+CD4- subpopulation and may exert effects on the subpopulations of both CD3+CD4+ and CD3+CD4- leukemia blast cells. When a TGFβR1 inhibitor, SB431542 was injected into the PtenΔ/Δ leukemic mice, the Smad3 and β-catenin expressions were down-regulated. On the basis of the results, we conclude that Miltefosine can suppress leukemia by degrading β-catenin through repression of the pT308-Akt and TGFβ1/Smad3 signaling pathways. This study demonstrates a possibility to inhibit Pten loss-associated leukemia genesis via targeting Akt and Smad3.
    Matched MeSH terms: Antineoplastic Agents/pharmacology
  7. Rabdosia rubescens Linn: green synthesis of gold nanoparticles and their anticancer effects against human lung cancer cells A549
    Zhang X, Tan Z, Jia K, Zhang W, Dang M
    Artif Cells Nanomed Biotechnol, 2019 Dec;47(1):2171-2178.
    PMID: 31159596 DOI: 10.1080/21691401.2019.1620249
    Nanomedicine is a rapidly emerging field and is reported to be a promising tool for treating various diseases. Green synthesized nanoparticles are documented to possess a potent anticancer effect. Rabdosia rubescens is a Chinese plant which is also one of the components of PC-SPES and used to treat prostate cancer. In the present study, we synthesized the gold nanoparticles from R. rubescens (RR-AuNP) and analyzed its anticancer activity against the lung carcinoma A549 cell lines. Since lung cancer is reported to be with increased morbidity and decreased survival rate. The biosynthesized RR-AuNP were confirmed using UV-Visible spectrophotometer, size and shape of RR-AuNP were assessed by DLS, TEM and EDX. The biomolecules present in RR-AuNP and its topographical structure were detected using FTIR, SAED and AFM analysis. MTT assay was performed to detect the IC50 dose of RR-AuNP and its apoptotic effect was assessed by detecting the caspases activation, ROS generation. The anticancer effect of RR-AuNP was confirmed by DAPI staining, TUNEL assay and its molecular mechanism were confirmed by assessing the apoptotic signalling molecules protein expression. Our results illustrate that RR-AuNP showed a strong absorption peak at 550 nm and the RRAuNP were polydispersed nanospheres with size of 130 nm. RR-AuNP IC50 dose against A549 lung carcinoma cell line was detected to be at 25 µg/ml. The results of DAPI staining, TUNEL and immunoblotting analysis confirms both the 25 µg/ml and 50 µg/ml of RR-AuNP possess potent anticancer and apoptotic effect, suggesting that RR-AuNP that it may be a persuasive molecule to treat lung cancer.
    Matched MeSH terms: Antineoplastic Agents/pharmacology
  8. Fulltext Synthesis of gold nanoparticles with Solanum xanthocarpum extract and their in vitro anticancer potential on nasopharyngeal carcinoma cells
    Zhang P, Wang P, Yan L, Liu L
    Int J Nanomedicine, 2018;13:7047-7059.
    PMID: 30464458 DOI: 10.2147/IJN.S180138
    BACKGROUND: Nasopharyngeal cancer (NPC) is one of the subtypes of head and neck cancers. It occurs rarely, and its prevalence depends mainly on geographical location. Modern-day research is focused on coupling nanotechnology and traditional medicine for combating cancers. Gold nanoparticles (AuNPs) were synthesized from Solanum xanthocarpum (Sx) leaf extract using reduction method.

    METHODS: Characterization of the synthesized AuNPs was done by different techniques such as ultraviolet-visible spectrum absorption, X-ray diffraction, dynamic light scattering, Fourier transform infrared spectroscopy, transmission electron microscopy, and energy-dispersive X-ray analysis.

    RESULTS: All the results showed the successful green synthesis of AuNPs from Sx, which induced apoptosis of C666-1 cell line (NPC cell line). There was a decline in both cell viability and colony formation in C666-1 cells upon treatment with Sx-AuNPs. The cell death was proved to be caused by autophagy and mitochondrial-dependent apoptotic pathway.

    CONCLUSION: Thus, due to their anticancer potential, these nanoparticles coupled with Sx can be used for in vivo applications and clinical research in future.

    Matched MeSH terms: Antineoplastic Agents/pharmacology
  9. Fulltext 10H-3,6-Diazaphenothiazine induces G2/M phase cell cycle arrest and caspase-dependent apoptosis and inhibits cell invasion of A2780 ovarian carcinoma cells through the regulation of NF-κB and (BIRC6-XIAP) complexes
    Zhang J, Ming C, Zhang W, Okechukwu PN, Morak-Młodawska B, Pluta K, et al.
    Drug Des Devel Ther, 2017;11:3045-3063.
    PMID: 29123378 DOI: 10.2147/DDDT.S144415
    The asymptomatic properties and high treatment resistance of ovarian cancer result in poor treatment outcomes and high mortality rates. Although the fundamental chemotherapy provides promising anticancer activities, it is associated with severe side effects. The derivative of phenothiazine, namely, 10H-3,6-diazaphenothiazine (PTZ), was synthesized and reported with ideal anticancer effects in a previous paper. In this study, detailed anticancer properties of PTZ was examined on A2780 ovarian cancer cells by investigating the cytotoxicity profiles, mechanism of apoptosis, and cell invasion. Research outcomes revealed PTZ-induced dose-dependent inhibition on A2780 cancer cells (IC50 =0.62 µM), with significant less cytotoxicity toward HEK293 normal kidney cells and H9C2 normal heart cells. Generation of reactive oxygen species (ROS) and polarization of mitochondrial membrane potential (ΔΨm) suggests PTZ-induced cell death through oxidative damage. The RT2 Profiler PCR Array on apoptosis pathway demonstrated PTZ-induced apoptosis via intrinsic (mitochondria-dependent) and extrinsic (cell death receptor-dependent) pathway. Inhibition of NF-κB and subsequent inhibition of (BIRC6-XIAP) complex activities reduced the invasion rate of A2780 cancer cells penetrating through the Matrigel™ Invasion Chamber. Lastly, the cell cycle analysis hypothesizes that the compound is cytostatic and significantly arrests cell proliferation at G2/M phase. Hence, the exploration of the underlying anticancer mechanism of PTZ suggested its usage as promising chemotherapeutic agent.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  10. Fulltext New generation of drug delivery systems based on ginsenoside Rh2-, Lysine- and Arginine-treated highly porous graphene for improving anticancer activity
    Zare-Zardini H, Taheri-Kafrani A, Amiri A, Bordbar AK
    Sci Rep, 2018 01 12;8(1):586.
    PMID: 29330486 DOI: 10.1038/s41598-017-18938-y
    In this study, Rh2-treated graphene oxide (GO-Rh2), lysine-treated highly porous graphene (Gr-Lys), arginine-treated Gr (Gr-Arg), Rh2-treated Gr-Lys (Gr-Lys-Rh2) and Rh2-treated Gr-Arg (Gr-Arg-Rh2) were synthesized. MTT assay was used for evaluation of cytotoxicity of samples on ovarian cancer (OVCAR3), breast cancer (MDA-MB), Human melanoma (A375) and human mesenchymal stem cells (MSCs) cell lines. The percentage of apoptotic cells was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. The hemolysis and blood coagulation activity of nanostructures were performed. Interestingly, Gr-Arg, Gr-Lys, Gr-Arg-Rh2, and Gr-Lys-Rh2 were more active against cancer cell lines in comparison with their cytotoxic activity against normal cell lines (MSCs) with IC50 values higher than 100 μg/ml. The results of TUNEL assay indicates a significant increase in the rates of TUNEL positive cells by increasing the concentrations of nanomaterials. Results were also shown that aggregation and changes of RBCs morphology were occurred in the presence of GO, GO-Rh2, Gr-Arg, Gr-Lys, Gr-Arg-Rh2, and Gr-Lys-Rh2. Note that all the samples had effect on blood coagulation system, especially on PTT. All nanostrucure act as antitumor drug so that binding of drugs to a nostructures is irresolvable and the whole structure enter to the cell as a drug.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  11. Fulltext Anti-Uterine Fibroid Effect of Standardized Labisia Pumila Var. Alata Extracts In Vitro and in Human Uterine Fibroid Cancer Xenograft Model
    Zakaria N, Mohd KS, Ahmed Saeed MA, Ahmed Hassan LE, Shafaei A, Al-Suede FSR, et al.
    Asian Pac J Cancer Prev, 2020 Apr 01;21(4):943-951.
    PMID: 32334454 DOI: 10.31557/APJCP.2020.21.4.943
    BACKGROUND: Uterine fibroids are a common type of solid tumor presenting in women of reproductive age. There are very few alternative treatment available from conventional treatment involving surgeries. Labisia pumila var. alata or locally known as 'Kacip Fatimah' was widely used as traditional medicine in Malaysia. This plant has been used to maintain a healthy female reproductive system. The present study aimed to evaluate anti fibroid potential of L. pumila extracts through in vitro apoptosis activity against uterine leiomyoma cells (SK-UT-1) and in uterine leiomyoma xenograft model. Evaluation of bioactive markers content were also carried out.

    METHODS: Apoptotic induction of the extracts was determined by morphological examination of AO/PI dual staining assay by flourescent microscopy and flow cytometry analysis on Annexin V-FITC/PI stained cells. In vivo study was done in immune-compromised mouse xenograft model. HPLC analysis was employed to quantify marker compounds.

    RESULTS: Morphological analysis showed L. pumila induced apoptosis in a dose dependent manner against SK-UT-1 cells. In vivo study indicated that L. pumila significantly suppressed the growth of uterine fibroid tumor. All tested extracts contain bioactive marker of gallic acid and cafeic acid.

    CONCLUSION: This work provide significant data of the potential of L. pumila in management of uterine fibroids.
    .

    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  12. Fulltext Cytotoxic, Anti-Proliferative and Apoptosis Activity of l-Amino Acid Oxidase from Malaysian Cryptelytrops purpureomaculatus (CP-LAAO) Venom on Human Colon Cancer Cells
    Zainal Abidin SA, Rajadurai P, Hoque Chowdhury ME, Othman I, Naidu R
    Molecules, 2018 06 08;23(6).
    PMID: 29890640 DOI: 10.3390/molecules23061388
    The aim of this study is to investigate the potential anti-cancer activity of l-amino acid oxidase (CP-LAAO) purified from the venom of Cryptelytrops purpureomaculatus on SW480 and SW620 human colon cancer cells. Mass spectrometry guided purification was able to identify and purify CP-LAAO. Amino acid variations identified from the partial protein sequence of CP-LAAO may suggest novel variants of these proteins. The activity of the purified CP-LAAO was confirmed with o-phenyldiamine (OPD)-based spectrophotometric assay. CP-LAAO demonstrated time- and dose-dependent cytotoxic activity and the EC50 value was determined at 13 µg/mL for both SW480 and SW620 cells. Significant increase of caspase-3 activity, reduction of Bcl-2 levels, as well as morphological changes consistent with apoptosis were demonstrated by CP-LAAO. Overall, these data provide evidence on the potential anti-cancer activity of CP-LAAO from the venom of Malaysian C. purpureomaculatus for therapeutic intervention of human colon cancer.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  13. Synthesis of Apoptotic New Quinazolinone-Based Compound and Identification of its Underlying Mitochondrial Signalling Pathway in Breast Cancer Cells
    Zahedifard M, Faraj FL, Paydar M, Looi CY, Hasandarvish P, Hajrezaie M, et al.
    Curr Pharm Des, 2015;21(23):3417-26.
    PMID: 25808938
    The anti-carcinogenic effect of the new quinazolinone compound, named MMD, was tested on MCF-7 human breast cancer cell line. The synthesis of quinazolinone-based compounds attracted strong attention over the past few decades as an alternative mean to produce analogues of natural products. Quinazolinone compounds sharing the main principal core structures are currently introduced in the clinical trials and pharmaceutical markets as anti-cancer agents. Thus, it is of high clinical interest to identify a new drug that could be used to control the growth and expansion of cancer cells. Quinazolinone is a metabolite derivative resulting from the conjugation of 2-aminobenzoyhydrazide and 5-methoxy-2- hydroxybenzaldehyde based on condensation reactions. In the present study, we analysed the influence of MMD on breast cancer adenoma cell morphology, cell cycle arrest, DNA fragmentation, cytochrome c release and caspases activity. MCF-7 is a type of cell line representing the breast cancer adenoma cells that can be expanded and differentiated in culture. Using different in vitro strategies and specific antibodies, we demonstrate a novel role for MMD in the inhibition of cell proliferation and initiation of the programmed cell death. MMD was found to increase cytochrome c release from the mitochondria to the cytosol and this effect was enhanced over time with effective IC50 value of 5.85 ± 0.71 μg/mL detected in a 72-hours treatment. Additionally, MMD induced cell cycle arrest at G0/G1 phase and caused DNA fragmentation with obvious activation of caspase-9 and caspases-3/7. Our results demonstrate a novel role of MMD as an anti-proliferative agent and imply the involvement of mitochondrial intrinsic pathway in the observed apoptosis.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  14. Pd(II) complexes with chelating N-(1-alkylpyridin-4(1H)-ylidene)amide (PYA) ligands: Synthesis, characterization and evaluation of anticancer activity
    Zafar MN, Butt AM, Chaudhry GE, Perveen F, Nazar MF, Masood S, et al.
    J Inorg Biochem, 2021 11;224:111590.
    PMID: 34507110 DOI: 10.1016/j.jinorgbio.2021.111590
    The bidentate N-(1-Alkylpyridin-4(1H)-ylidene)amide (PYA) pro-ligands [H2LBn][Cl]2 (2), and [H2LMe][TfO]2 (3) were prepared by simple alkylation reactions of the known compound, N,N-di(pyridin-4-yl)oxalamide (H2L, 1). The Pd(II) complexes, [Pd(LBn)2][Cl]2 (4), [Pd(LMe)2][Cl][TfO] (5), Pd(LBn)Cl2 (6) and Pd(LMe)Cl2 (7) were synthesized through reactions between these pro-ligands and suitable Pd(II) substrates in the presence of base. The molecular structures of 3 and 6 were obtained by single crystal X-ray structure determinations. Studies of the experimental and computational DNA binding interactions of the compounds 1-7 revealed that overall 4 and 6 have the largest values for the binding parameters Kb and ΔGbo. The results showed a good correlation with the steric and electronic parameters obtained by quantitative structure activity relationship (QSAR) studies. In-vitro cytotoxicity studies against four different cell lines showed that the human breast cancer cell lines MCF-7, T47D and cervical cancer cell line HeLa had either higher or similar sensitivities towards 4, 6 and 2, respectively, compared to cisplatin. In general, the cytotoxicity of the compounds, represented by IC50 values, decreased in the order 4 > 6 > 2 > 5 > 3 > 1 > 7 in cancer cell lines. Apoptosis contributed significantly to the cytotoxic effects of these anticancer agents as evaluated by apoptosis studies.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  15. Fulltext Combining PARP Inhibition with Platinum, Ruthenium or Gold Complexes for Cancer Therapy
    Yusoh NA, Ahmad H, Gill MR
    ChemMedChem, 2020 Nov 18;15(22):2121-2135.
    PMID: 32812709 DOI: 10.1002/cmdc.202000391
    Platinum drugs are heavily used first-line chemotherapeutic agents for many solid tumours and have stimulated substantial interest in the biological activity of DNA-binding metal complexes. These complexes generate DNA lesions which trigger the activation of DNA damage response (DDR) pathways that are essential to maintain genomic integrity. Cancer cells exploit this intrinsic DNA repair network to counteract many types of chemotherapies. Now, advances in the molecular biology of cancer has paved the way for the combination of DDR inhibitors such as poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) and agents that induce high levels of DNA replication stress or single-strand break damage for synergistic cancer cell killing. In this review, we summarise early-stage, preclinical and clinical findings exploring platinum and emerging ruthenium anti-cancer complexes alongside PARPi in combination therapy for cancer and also describe emerging work on the ability of ruthenium and gold complexes to directly inhibit PARP activity.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  16. Fulltext Green Synthesis of Fe3O4 Nanoparticles Stabilized by a Garcinia mangostana Fruit Peel Extract for Hyperthermia and Anticancer Activities
    Yusefi M, Shameli K, Su Yee O, Teow SY, Hedayatnasab Z, Jahangirian H, et al.
    Int J Nanomedicine, 2021;16:2515-2532.
    PMID: 33824589 DOI: 10.2147/IJN.S284134
    INTRODUCTION: Fe3O4 nanoparticles (Fe3O4 NPs) with multiple functionalities are intriguing candidates for various biomedical applications.

    MATERIALS AND METHODS: This study introduced a simple and green synthesis of Fe3O4 NPs using a low-cost stabilizer of plant waste extract rich in polyphenols content with a well-known antioxidant property as well as anticancer ability to eliminate colon cancer cells. Herein, Fe3O4 NPs were fabricated via a facile co-precipitation method using the crude extract of Garcinia mangostana fruit peel as a green stabilizer at different weight percentages (1, 2, 5, and 10 wt.%). The samples were analyzed for magnetic hyperthermia and then in vitro cytotoxicity assay was performed.

    RESULTS: The XRD planes of the samples were corresponding to the standard magnetite Fe3O4 with high crystallinity. From TEM analysis, the green synthesized NPs were spherical with an average size of 13.42±1.58 nm and displayed diffraction rings of the Fe3O4 phase, which was in good agreement with the obtained XRD results. FESEM images showed that the extract covered the surface of the Fe3O4 NPs well. The magnetization values for the magnetite samples were ranging from 49.80 emu/g to 69.42 emu/g. FTIR analysis verified the functional groups of the extract compounds and their interactions with the NPs. Based on DLS results, the hydrodynamic sizes of the Fe3O4 nanofluids were below 177 nm. Furthermore, the nanofluids indicated the zeta potential values up to -34.92±1.26 mV and remained stable during four weeks of storage, showing that the extract favorably improved the colloidal stability of the Fe3O4 NPs. In the hyperthermia experiment, the magnetic nanofluids showed the acceptable specific absorption rate (SAR) values and thermosensitive performances under exposure of various alternating magnetic fields. From results of in vitro cytotoxicity assay, the killing effects of the synthesized samples against HCT116 colon cancer cells were mostly higher compared to those against CCD112 colon normal cells. Remarkably, the Fe3O4 NPs containing 10 wt.% of the extract showed a lower IC50 value (99.80 µg/mL) in HCT116 colon cancer cell line than in CCD112 colon normal cell line (140.80 µg/mL).

    DISCUSSION: This research, therefore, introduced a new stabilizer of Garcinia mangostana fruit peel extract for the biosynthesis of Fe3O4 NPs with desirable physiochemical properties for potential magnetic hyperthermia and colon cancer treatment.

    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  17. Anti-proliferative and pro-apoptotic effects from sequenced combinations of andrographolide and cisplatin on ovarian cancer cell lines
    Yunos NM, Mutalip SS, Jauri MH, Yu JQ, Huq F
    Anticancer Res, 2013 Oct;33(10):4365-71.
    PMID: 24123004
    Andrographolide (Andro) is a diterpenoid that is isolated from Andrographis paniculata and reported to be active against several cancer cell lines. However, few in-depth studies have been carried out on its effects on ovarian cancer cell lines alone or in combination with cisplatin (Cis), which is commonly used to treat ovarian cancer. The aim of this study was to determine the anti-proliferative and apoptotic effects of Andro administered alone and in combination with Cis in the ovarian A2780 and A2780(cisR) cancer cell lines using five different sequences of administration (Cis/Andro h): 0/0h, 4/0 h, 0/4 h, 24/0 h and 0/24 h. The results were evaluated in terms of medium-effect dose (Dm) and combination indices (CI) using the CalcuSyn software. Unlike Cis, whose activity was lower in the resistant A2780(cisR) cell line than in the parent A2780 cell line, Andro was found to be three times more active in the A2780(cisR) cell line as compared to that in A2780 cell line. Synergism was observed when Cis and Andro were administered using the sequences 0/4 h and 4/0 h. The percentage of apoptotic cell death was found to be greater for the 0/4 h combination of Andro and Cis as compared to those values from single-drug treatments. The results may be clinically significant if confirmed in vivo.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  18. Benzimidazoles as new scaffold of sirtuin inhibitors: green synthesis, in vitro studies, molecular docking analysis and evaluation of their anti-cancer properties
    Yoon YK, Ali MA, Wei AC, Shirazi AN, Parang K, Choon TS
    Eur J Med Chem, 2014 Aug 18;83:448-54.
    PMID: 24992072 DOI: 10.1016/j.ejmech.2014.06.060
    Two series of novel benzimidazole derivatives were designed, synthesized and evaluated for their SIRT1 and SIRT2 inhibitory activity. Among the newly synthesized compounds, compound 4j displayed the best inhibitory activity for SIRT1 (IC50 = 54.21 μM) as well as for SIRT2 (IC50 = 26.85 μM). Cell proliferation assay showed that compound 4j possessed good antitumor activity against three different types of cancer cells derived from colon (HCT-116), breast (MDA-MB-468) and blood-leukemia (CCRF-CEM) with cell viability of 40.0%, 53.2% and 27.2% respectively at 50 μM. Docking analysis of representative compound 4j into SIRT2 indicated that the interaction with receptor was primarily due to hydrogen bonding and π-π stacking interactions.
    Matched MeSH terms: Antineoplastic Agents/pharmacology
  19. Synthesis and evaluation of novel benzimidazole derivatives as sirtuin inhibitors with antitumor activities
    Yoon YK, Ali MA, Wei AC, Choon TS, Osman H, Parang K, et al.
    Bioorg Med Chem, 2014 Jan 15;22(2):703-10.
    PMID: 24387981 DOI: 10.1016/j.bmc.2013.12.029
    A total of 15 novel benzimidazole derivatives were designed, synthesized and evaluated for their SIRT1 and SIRT2 inhibitory activity. All compounds showed better inhibition on SIRT2 as compared to SIRT1. Among these, compound 5j displayed the best inhibitory activity for SIRT1 (IC50=58.43μM) as well as for SIRT2 (IC50=45.12μM). Cell cytotoxicity assays also showed that compound 5j possesses good antitumor activity against two different cancer cell lines derived from breast cancer (MCF-7 and MDA-MB-468). A simple structure-activity-relationship (SAR) study of the newly synthesized benzimidazole derivatives was also discussed.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  20. Anti-proliferative and anti-invasive properties of a purified fraction from Streptomyces sp. H7372
    Yip WK, Cheenpracha S, Chang LC, Ho CC, Seow HF
    Int J Oncol, 2010 Nov;37(5):1229-41.
    PMID: 20878070
    Secondary metabolites from actinomycetes especially the genus Streptomyces may be one of the most important sources for novel anticancer agents. A purified fraction from a novel actinomycete strain, Streptomyces sp. H7372, was elucidated in breast cancer cells. We have isolated three purified fractions from a novel strain, Streptomyces sp. H7372. One of the fractions, designated as 31-2, exhibited the strongest growth-inhibitory effect and thereby was selected for further studies. 31-2 exerted a growth-inhibitory effect on a panel of 15 human cancer and 2 non-malignant cell lines. In MCF-7 and MDA-MB-231 breast cancer cells, 31-2 induced a cytostatic (anti-proliferative) effect without causing cytotoxicity (cell death). Our data suggest that the cytostasis resulted from cell cycle arrest at the G1 phase in MCF-7 cells and at the S phase in MDA-MB-231 cells. Western blot analysis demonstrated a modulation of phosphorylation of the Rb and CDC2 proteins and of CDK4, cyclin D1 and cyclin D3 in the 31-2-treated breast cancer cell lines. The protein levels of CDK2, CDK6, and PCNA were not affected by 31-2 treatment. 31-2 also exhibited an anti-invasive effect in MDA-MB-231 cells. However, this effect is not attributed to the modulation of proteolytic activity in MDA-MB-231 cells as the enzymatic degradation of type IV collagen was not affected by 31-2. The 31-2 is a potent cytostatic and anti-invasive agent and modulates the cell cycle pathway. Together, these results will have important implications in searching for novel approaches to treat cancer.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links