Displaying publications 321 - 340 of 482 in total

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  1. Development of biodegradable sustained-release damnacanthal nanocapsules for potential application in in-vitro breast cancer studies
    Mohd MR, Ariff TM, Mohamad N, Abdul Latif AZ, Wan Nik WMN, Mohamed A, et al.
    Pak J Pharm Sci, 2019 Sep;32(5):2155-2162.
    PMID: 31813882
    The "noni" species of Morinda citrifolia L., is using in traditional medicine in the tropical country for over 2000 years. Noni fruit has come from the Morinda citrifolia tree which is called Rubiaceae, and it is from the coffee family. It is a perennial herb whose ripe fruit has a robust butyric acid smell and flavor. Recently scientists have proven that this fruit has antioxidant and antibiotic properties in vitro. An anthraquinone, damnacanthal, is one of the constituents of Morinda citrifolia. It has been demonstrated to have anti-cancer properties. Damnacanthal has low water solubility and low bioavailability. Formulating of damnacanthal into the biodegradable nanocapsule drug delivery system may increase its bioavailability. Various formulations of damnacanthal would be developed to enable the selection of a dosage form that could offer the provision of the anti-cancer bioactive substance with suitable sustained- or controlled release properties. The efficiency of extraction of damnacanthal will be compared using both conventional and traditional method. Both the damnacanthal and an anthraquinone active compounds extracted from noni roots, are currently being studied in the context of anti-cancer study. Soon, the medical values, bioactivities and nutritional of this fruit can be assessed, especially its anti-cancer activity, this fruit extract could play an outstanding economic role in Malaysia and other tropical countries.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  2. Fulltext Bromelain Enhances the Anti-tumor Effects of Cisplatin on 4T1 Breast Tumor Model In Vivo
    Mohamad NE, Abu N, Yeap SK, Alitheen NB
    Integr Cancer Ther, 2019 11 23;18:1534735419880258.
    PMID: 31752555 DOI: 10.1177/1534735419880258
    Background: This study aimed to evaluate the antitumor enhancing effect of bromelain consumption on 4T1-challenged mice treated with cisplatin. Methods: Mice challenged with 4T1 triple-negative breast cancer cells received water, bromelain, cisplatin, or bromelain + cisplatin treatment for 28 days. Tumor size was measured, and lung metastasis was evaluated by clonogenic assay. Expression of tumor inflammatory genes of the harvested tumor was quantified by polymerase chain reaction array and ELISA (enzyme-linked immunosorbent assay). Results: All treatments significantly reduced the size of tumor and lung metastasis, with combination treatment showing the best effect. Also, bromelain alone and combination treatment showed downregulation of the expression of tumor inflammatory genes (Gremlin [GREM1], interleukin 1β [IL-1β], interleukin-4 [IL-4], nuclear factor κB subunit 1 [NFκB1], and prostaglandin-endoperoxide synthase 2 [PTGS2]), tumor nitric oxide level, and serum IL-1β, and IL-4 levels. On the other hand, cisplatin treatment increased the expression of selected inflammatory markers. Conclusion: This study suggests that bromelain treatment could potentiate the antitumor effect of cisplatin on triple-negative breast cancer 4T1 cells through modulating the tumor environmental inflammation.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  3. Fulltext Anti-Cancer Effects of Synergistic Drug-Bacterium Combinations on Induced Breast Cancer in BALB/c Mice
    Subramaniam M, Arshad NM, Mun KS, Malagobadan S, Awang K, Nagoor NH
    Biomolecules, 2019 10 18;9(10).
    PMID: 31635311 DOI: 10.3390/biom9100626
    Cancer development and progression are extremely complex due to the alteration of various genes and pathways. In most cases, multiple agents are required to control cancer progression. The purpose of this study is to investigate, using a mouse model, the synergistic interactions of anti-cancer agents, 1'-S-1'-acetoxychavicol acetate (ACA), Mycobacterium indicus pranii (MIP), and cisplatin (CDDP) in double and triple combinations to treat chemo-sensitize and immune-sensitize breast cancer. Changes in tumor volume and body weight were monitored. Organs were harvested and stained using hematoxylin-eosin for histopathological assessment. Milliplex enzyme-linked immunosorbent assay (ELISA) was performed to determine cytokine levels, while immunohistochemistry (IHC) was conducted on tumor biopsies to verify systemic drug effects. In vivo mouse models showed tumor regression with maintenance of regular body weight for all the different treatment regimens. IHC results provided conclusive evidence indicating that combination regimens were able to down-regulate nuclear factor kappa-B activation and reduce the expression of its regulated pro-inflammatory proteins. Reduction of pro-inflammatory cytokines (e.g., IL-6, TNF-α, and IFN-ɣ) levels were observed when using the triple combination, which indicated that the synergistic drug combination was able to significantly control cancer progression. In conclusion, ACA, MIP, and CDDP together serve as promising candidates for further development and for subsequent clinical trials against estrogen-sensitive breast cancer.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  4. Methadone hydrochloride and leukemia cells: Effects on cell viability, DNA fragmentation and apoptotic proteins expression level
    Kua VMD, Rasul A, Sreenivasan S, Rasool B, Younis T, Lai NS
    Pak J Pharm Sci, 2019 Jul;32(4(Supplementary)):1797-1803.
    PMID: 31680075
    Leukemia is a type of blood cancer where abnormal and immature leucocytes are produced in the bone marrow. Methadone hydrochloride is a man-made drug that is commonly used in the maintenance treatment for drug addiction. The objective of this research was to determine the cytotoxic activity and apoptotic effects of methadone hydrochloride treatment towards two leukemia cell lines which are CCRF-CEM and HL-60. CCRF-CEM and HL-60 cells were treated with methadone hydrochloride for 24 and 48 hours to determine the cytotoxic activity. IC50 at 24 hours obtained for CCRF-CEM was 121.6μmol/L while IC50 for HL-60 cells was 97.18μmol/L. Result obtained from DNA fragmentation assay showed no characteristic DNA ladder pattern in CCRF-CEM leukemia cells treated with methadone hydrochloride. Characteristics DNA ladder pattern was observed in methadone hydrochloride treated HL-60 cells. Formation of comets was seen in methadone hydrochloride treated CCRF-CEM and HL-60 cells with varying degree of DNA damage. The comets formed by methadone hydrochloride treated HL-60 cells were more prominent as compared to methadone-treated CCRF-CEM cells. The expression of apoptotic-related proteins in methadone-treated CCRF-CEM and HL-60 cells were checked by incubating the cell lysate with Raybio® Human Apoptosis Antibody Array. Significant alterations in expression level of apoptosis-related proteins in methadone hydrochloride treated CCRF-CEM cells were found involving upregulation of caspase-8 expression and downregulation of survivin expression. Methadone hydrochloride induced apoptosis in HL-60 cells involved upregulation of Bid and caspase-8 expression and downregulation of Bcl-2, p21 and survivin expression.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  5. Enhanced photocatalysis and anticancer activity of green hydrothermal synthesized Ag@TiO2 nanoparticles
    Hariharan D, Thangamuniyandi P, Jegatha Christy A, Vasantharaja R, Selvakumar P, Sagadevan S, et al.
    J. Photochem. Photobiol. B, Biol., 2020 Jan;202:111636.
    PMID: 31739259 DOI: 10.1016/j.jphotobiol.2019.111636
    Titanium dioxide (TiO2) nanoparticles (NPs) have been doped with varying amounts (0.005, 0.010 and 0.015 M) of silver nanoparticles (Ag NPs) using hydrothermal method. Further, in this work, a green approach was followed for the formation of Ag@TiO2 NPs using Aloe vera gel as a capping and reducing agent. The structural property confirmed the presence of anatase phase TiO2. Increased peak intensity was observed while increasing the Ag concentration. Further, the morphological and optical properties have been studied, which confirmed the effective photocatalytic behavior of the prepared Ag@TiO2 NPs. The photocatalytic performance of Ag@TiO2 has been considered for the degradation of picric acid in the visible light region. The concentration at 0.010 M of the prepared Ag@TiO2 has achieved higher photocatalytic performance within 50 min, which could be attributed to its morphological behavior. Similarly, anticancer activity against lung cancer cell lines (A549) was also determined. The Ag@TiO2 NPs generated a large quantity of reactive oxygen species (ROS), resulting in complete cancer cell growth suppression after their systemic in vitro administration. Ag@TiO2 NPs was adsorbed visible light that leads to an enhanced anticancer sensitivity by killing and inhibiting cancer cell reproduction through cell viability assay test. It was clear that 0.015 M of Ag@TiO2 NPs were highly effective against human lung cancer cell lines and showed increased production of ROS in cancer cell lines due to the medicinal behavior of the Aloe vera gel.
    Matched MeSH terms: Antineoplastic Agents/pharmacology
  6. Novel 9-(2-(1-arylethylidene)hydrazinyl)acridine derivatives: Target Topoisomerase 1 and growth inhibition of HeLa cancer cells
    Haider MR, Ahmad K, Siddiqui N, Ali Z, Akhtar MJ, Fuloria N, et al.
    Bioorg Chem, 2019 07;88:102962.
    PMID: 31085373 DOI: 10.1016/j.bioorg.2019.102962
    A series of 9-(2-(1-arylethylidene)hydrazinyl)acridine and its analogs were designed, synthesized and evaluated for biological activities. Various biochemical assays were performed to determine the free radical scavenging capacity of synthesized compounds (4a-4j). Anticancer activity of these compounds was assessed against two different human cancer cell lines viz cervical cancer cells (HeLa) and liver cancer cells (HepG2) as well as normal human embryonic kidney cell line (HEK 293). Compounds 4b, 4d and 4e showed potential anti-proliferative effects on HeLa cells. Based on results obtained from antioxidant and cytotoxicity studies, 4b, 4d and 4e were further studied in detail for different biological activities. 4b, 4d and 4e reduced the cell growth, inhibited metastatic activity and declined the potential of cell migration in HeLa cell lines. Topoisomerase1 (Top1) treated with compounds 4b, 4d and 4e exhibited inhibition of Top1 and prevented DNA replication. Molecular docking results validate that interaction of compounds 4b, 4d and 4e with Top1-DNA complex, which might be accountable for their inhibitory effects. Further it was concluded that compounds 4b, 4d and 4e arrests the cells at S phase and consequently induces cell death through DNA damage in HeLa cells.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  7. Fulltext Streptomyces monashensis sp. nov., a novel mangrove soil actinobacterium from East Malaysia with antioxidative potential
    Law JW, Ser HL, Ab Mutalib NS, Saokaew S, Duangjai A, Khan TM, et al.
    Sci Rep, 2019 02 28;9(1):3056.
    PMID: 30816228 DOI: 10.1038/s41598-019-39592-6
    A new Streptomyces species discovered from Sarawak mangrove soil is described, with the proposed name - Streptomyces monashensis sp. nov. (strain MUSC 1JT). Taxonomy status of MUSC 1JT was determined via polyphasic approach. Phylogenetic and chemotaxonomic properties of strain MUSC 1JT were in accordance with those known for genus Streptomyces. Based on phylogenetic analyses, the strains closely related to MUSC 1JT were Streptomyces corchorusii DSM 40340T (98.7%), Streptomyces olivaceoviridis NBRC 13066T (98.7%), Streptomyces canarius NBRC 13431T (98.6%) and Streptomyces coacervatus AS-0823T (98.4%). Outcomes of DNA-DNA relatedness between strain MUSC 1JT and its closely related type strains covered from 19.7 ± 2.8% to 49.1 ± 4.3%. Strain MUSC 1JT has genome size of 10,254,857 bp with DNA G + C content of 71 mol%. MUSC 1JT extract exhibited strong antioxidative activity up to 83.80 ± 4.80% in the SOD assay, with significant cytotoxic effect against colon cancer cell lines HCT-116 and SW480. Streptomyces monashensis MUSC 1JT (=DSM 103626T = MCCC 1K03221T) could potentially be a producer of novel bioactive metabolites; hence discovery of this new species may be highly significant to the biopharmaceutical industry as it could lead to development of new and useful chemo-preventive drugs.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  8. Synthesis and characterization of gold nanoparticles from aqueous leaf extract of Alternanthera sessilis and its anticancer activity on cervical cancer cells (HeLa)
    Qian L, Su W, Wang Y, Dang M, Zhang W, Wang C
    Artif Cells Nanomed Biotechnol, 2019 Dec;47(1):1173-1180.
    PMID: 30942109 DOI: 10.1080/21691401.2018.1549064
    Cervical cancer is the third most common highest mortality in women worldwide. The use of standard chemotherapeutic drugs against cervical cancer patients received several side effects. Therefore, we focused phytoconsituents-mediated synthesis of gold nanoparticles (AuNPs) considered as greatest attention in the treatment of cervical cancer. In this present study, we reported that green synthesis of AuNPs by using with Alternanthera Sessilis aqueous extract. Synthesis of AuNPs were characterized by UV visible spectroscopy, energy dispersive X-ray (EDX), selected area diffraction pattern (SAED), Fourier transform infrared spectroscopy (FTIR), high-resolution transmission electron microscopy (HR-TEM) and atomic force microscope. Synthesized AuNPs confirmed by the UV absorption maximum at 535 and crystal structure of gold AuNPs was further confirmed by EDX and SAED. TEM and atomic force microscopy images show the size and morphological distribution of nanoparticles. FTIR analysis was confirmed the hydroxyl groups, amine and alkaline groups of biomolecules are present in the AuNPs. Moreover, AuNPs induce cytotoxicity in cervical cancer cells and also induce apoptosis through modulating intrinsic apoptotic mechanisms in cervical cancer cells. This green synthesis of AuNPs from Alternanthera sessilis approach was easy, large scaled up and eco-friendly.
    Matched MeSH terms: Antineoplastic Agents/pharmacology
  9. Fulltext In vitro cytotoxicity and anticancer effects of citral nanostructured lipid carrier on MDA MBA-231 human breast cancer cells
    Nordin N, Yeap SK, Rahman HS, Zamberi NR, Abu N, Mohamad NE, et al.
    Sci Rep, 2019 02 07;9(1):1614.
    PMID: 30733560 DOI: 10.1038/s41598-018-38214-x
    Very recently, we postulated that the incorporation of citral into nanostructured lipid carrier (NLC-Citral) improves solubility and delivery of the citral without toxic effects in vivo. Thus, the objective of this study is to evaluate anti-cancer effects of NLC-Citral in MDA MB-231 cells in vitro through the Annexin V, cell cycle, JC-1 and fluorometric assays. Additionally, this study is aimed to effects of NLC-Citral in reducing the tumor weight and size in 4T1 induced murine breast cancer model. Results showed that NLC-Citral induced apoptosis and G2/M arrest in MDA MB-231 cells. Furthermore, a prominent anti-metastatic ability of NLC-Citral was demonstrated in vitro using scratch, migration and invasion assays. A significant reduction of migrated and invaded cells was observed in the NLC-Citral treated MDA MB-231 cells. To further evaluate the apoptotic and anti-metastatic mechanism of NLC-Citral at the molecular level, microarray-based gene expression and proteomic profiling were conducted. Based on the result obtained, NLC-Citral was found to regulate several important signaling pathways related to cancer development such as apoptosis, cell cycle, and metastasis signaling pathways. Additionally, gene expression analysis was validated through the targeted RNA sequencing and real-time polymerase chain reaction. In conclusion, the NLC-Citral inhibited the proliferation of breast cancer cells in vitro, majorly through the induction of apoptosis, anti-metastasis, anti-angiogenesis potentials, and reducing the tumor weight and size without altering the therapeutic effects of citral.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  10. 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
  11. New One-Pot Synthesis of 1,3,5-Triazines: Three-Component Condensation, Dimroth Rearrangement, and Dehydrogenative Aromatization
    Junaid A, Lim FPL, Tiekink ERT, Dolzhenko AV
    ACS Comb Sci, 2019 07 08;21(7):548-555.
    PMID: 31180634 DOI: 10.1021/acscombsci.9b00079
    A new, effective one-pot synthesis of the 6, N2-diaryl-1,3,5-triazine-2,4-diamines under microwave irradiation was developed. The method involved an initial three-component condensation of cyanoguanidine, aromatic aldehydes, and arylamines in the presence of hydrochloric acid. Without isolation, the resulting 1,6-diaryl-1,6-dihydro-1,3,5-triazine-2,4-diamines were treated with a base to initiate Dimroth rearrangement and spontaneous dehydrogenative aromatization, affording the desired compounds. The developed method was found to be sufficiently general in scope, tolerating various aromatic aldehydes and amines; by using their combinations in the first step, a representative library of 110 compounds was successfully prepared and screened for anticancer properties.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  12. Fulltext Small Molecules Targeting Programmed Cell Death in Breast Cancer Cells
    Maniam S, Maniam S
    Int J Mol Sci, 2021 Sep 08;22(18).
    PMID: 34575883 DOI: 10.3390/ijms22189722
    Targeted chemotherapy has become the forefront for cancer treatment in recent years. The selective and specific features allow more effective treatment with reduced side effects. Most targeted therapies, which include small molecules, act on specific molecular targets that are altered in tumour cells, mainly in cancers such as breast, lung, colorectal, lymphoma and leukaemia. With the recent exponential progress in drug development, programmed cell death, which includes apoptosis and autophagy, has become a promising therapeutic target. The research in identifying effective small molecules that target compensatory mechanisms in tumour cells alleviates the emergence of drug resistance. Due to the heterogenous nature of breast cancer, various attempts were made to overcome chemoresistance. Amongst breast cancers, triple negative breast cancer (TNBC) is of particular interest due to its heterogeneous nature in response to chemotherapy. TNBC represents approximately 15% of all breast tumours, however, and still has a poor prognosis. Unlike other breast tumours, signature targets lack for TNBCs, causing high morbidity and mortality. This review highlights several small molecules with promising preclinical data that target autophagy and apoptosis to induce cell death in TNBC cells.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  13. Fulltext Cytotoxic and radiosensitising effects of a novel thioredoxin reductase inhibitor in breast cancer
    Abdullah NA, Inman M, Moody CJ, Storr SJ, Martin SG
    Invest New Drugs, 2021 10;39(5):1232-1241.
    PMID: 33768386 DOI: 10.1007/s10637-021-01106-5
    Radiotherapy is an effective treatment modality for breast cancer but, unfortunately, not all patients respond fully with a significant number experiencing local recurrences. Overexpression of thioredoxin and thioredoxin reductase has been reported to cause multidrug and radiation resistance - their inhibition may therefore improve therapeutic efficacy. Novel indolequinone compounds have been shown, in pancreatic cancer models, to inhibit thioredoxin reductase activity and exhibit potent anticancer activity. The present study evaluates, using in vitro breast cancer models, the efficacy of a novel indolequinone compound (IQ9) as a single agent and in combination with ionising radiation using a variety of endpoint assays including cell proliferation, clonogenic survival, enzyme activity, and western blotting. Three triple-negative breast cancer (MDA-MB-231, MDA-MB-468, and MDA-MB-436) and two luminal (MCF-7 and T47D) breast cancer cell lines were used. Results show that treatment with IQ9 significantly inhibited thioredoxin reductase activity, and inhibited cell growth and colony formation of breast cancer cells with IC50 values in the low micromolar ranges. Enhanced radiosensitivity of triple-negative breast cancer cells was observed, with sensitiser enhancement ratios of 1.20-1.43, but with no evident radiosensitisation of luminal breast cancer cell lines. IQ9 upregulated protein expression of thioredoxin reductase in luminal but not in triple-negative breast cancer cells which may explain the observed differential radiosensitisation. This study provides important evidence of the roles of the thioredoxin system as an exploitable radiobiological target in breast cancer cells and highlights the potential therapeutic value of indolequinones as radiosensitisers.***This study was not part of a clinical trial. Clinical trial registration number: N/A.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  14. 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*
  15. Fulltext Protective effect of curcumin against ultraviolet A irradiation‑induced photoaging in human dermal fibroblasts
    Liu X, Zhang R, Shi H, Li X, Li Y, Taha A, et al.
    Mol Med Rep, 2018 05;17(5):7227-7237.
    PMID: 29568864 DOI: 10.3892/mmr.2018.8791
    Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in skin, resulting in photoaging. Natural botanicals have gained considerable attention due to their beneficial protection against the harmful effects of UV irradiation. The present study aimed to evaluate the ability of curcumin (Cur) to protect human dermal fibroblasts (HDFs) against ultraviolet A (UVA)‑induced photoaging. HDFs were treated with 0‑10 µM Cur for 2 h and subsequently exposed to various intensities of UVA irradiation. The cell viability and apoptotic rate of HDFs were investigated by MTT and flow cytometry assays, respectively. The effect of UVA and Cur on the formation of reactive oxygen species (ROS), malondialdehyde levels, which are an indicator of ROS, and the levels/activity of antioxidative defense proteins, including glutathione, superoxide dismutase and catalase, were evaluated using 2',7'-dichlorofluorescin diacetate and commercial assay kits. Furthermore, western blotting was performed to determine the levels of proteins associated with endoplasmic reticulum (ER) stress, the apoptotic pathway, inflammation and the collagen synthesis pathway. The results demonstrated that Cur reduced the accumulation of ROS and restored the activity of antioxidant defense enzymes, indicating that Cur minimized the damage induced by UVA irradiation in HDFs. Furthermore, western blot analysis demonstrated that Cur may attenuate UVA‑induced ER stress, inflammation and apoptotic signaling by downregulating the protein expression of glucose‑regulated protein 78, C/EBP‑homologous protein, nuclear factor‑κB and cleaved caspase‑3, while upregulating the expression of Bcl‑2. Additionally, it was demonstrated that Cur may regulate collagen metabolism by decreasing the protein expression of matrix metalloproteinase (MMP)‑1 and MMP‑3, and may promote the repair of cells damaged as a result of UVA irradiation through increasing the protein expression of transforming growth factor‑β (TGF‑β) and Smad2/3, and decreasing the expression of the TGF‑β inhibitor, Smad7. In conclusion, the results of the present study indicate the potential benefits of Cur for the protection of HDFs against UVA‑induced photoaging and highlight the potential for the application of Cur in skin photoprotection.
    Matched MeSH terms: Antineoplastic Agents/pharmacology
  16. Fulltext Molecular Mechanisms of Antiproliferative and Apoptosis Activity by 1,5-Bis(4-Hydroxy-3-Methoxyphenyl)1,4-Pentadiene-3-one (MS13) on Human Non-Small Cell Lung Cancer Cells
    Wan Mohd Tajuddin WNB, Abas F, Othman I, Naidu R
    Int J Mol Sci, 2021 Jul 10;22(14).
    PMID: 34299042 DOI: 10.3390/ijms22147424
    Diarylpentanoid (DAP), an analog that was structurally modified from a naturally occurring curcumin, has shown to enhance anticancer efficacy compared to its parent compound in various cancers. This study aims to determine the cytotoxicity, antiproliferative, and apoptotic activity of diarylpentanoid MS13 on two subtypes of non-small cell lung cancer (NSCLC) cells: squamous cell carcinoma (NCI-H520) and adenocarcinoma (NCI-H23). Gene expression analysis was performed using Nanostring PanCancer Pathways Panel to determine significant signaling pathways and targeted genes in these treated cells. Cytotoxicity screening revealed that MS13 exhibited greater inhibitory effect in NCI-H520 and NCI-H23 cells compared to curcumin. MS13 induced anti-proliferative activity in both cells in a dose- and time-dependent manner. Morphological analysis revealed that a significant number of MS13-treated cells exhibited apoptosis. A significant increase in caspase-3 activity and decrease in Bcl-2 protein concentration was noted in both MS13-treated cells in a time- and dose-dependent manner. A total of 77 and 47 differential expressed genes (DEGs) were regulated in MS13 treated-NCI-H520 and NCI-H23 cells, respectively. Among the DEGs, 22 were mutually expressed in both NCI-H520 and NCI-H23 cells in response to MS13 treatment. The top DEGs modulated by MS13 in NCI-H520-DUSP4, CDKN1A, GADD45G, NGFR, and EPHA2-and NCI-H23 cells-HGF, MET, COL5A2, MCM7, and GNG4-were highly associated with PI3K, cell cycle-apoptosis, and MAPK signaling pathways. In conclusion, MS13 may induce antiproliferation and apoptosis activity in squamous cell carcinoma and adenocarcinoma of NSCLC cells by modulating DEGs associated with PI3K-AKT, cell cycle-apoptosis, and MAPK pathways. Therefore, our present findings could provide an insight into the anticancer activity of MS13 and merits further investigation as a potential anticancer agent for NSCLC cancer therapy.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  17. Generation of osimertinib-resistant cells from epidermal growth factor receptor L858R/T790M mutant non-small cell lung carcinoma cell line
    Verusingam ND, Chen YC, Lin HF, Liu CY, Lee MC, Lu KH, et al.
    J Chin Med Assoc, 2021 03 01;84(3):248-254.
    PMID: 33009209 DOI: 10.1097/JCMA.0000000000000438
    BACKGROUND: Lung cancer contributes to high cancer mortality worldwide with 80% of total cases diagnosed as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase (TK) domain serves as a druggable target in NSCLC patients with exon 19 deletion and L858R mutation. However, patients eventually succumbed to resistance to first- and second-generation EGFR-TK inhibitors through activation of T790M mutation. Third-generation EGFR-TKI, Osimertinib exhibits high efficacy in patients with exon 19 deletion/L858R/T790M mutation but they experienced acquired resistance thereafter. Available treatment options in NSCLC patients remains a challenge due to unknown molecular heterogeneity responsible for acquired resistance to EGFR-TKI. In this study, we aim to generate Osimertinib-resistant (OR) cells from H1975 carrying L858R/T790M double mutation which can be used as a model to elucidate mechanism of resistance.

    METHODS: OR cells were established via stepwise-dose escalation and limiting single-cell dilution method. We then evaluated Osimertinib resistance potential via cell viability assay. Proteins expression related to EGFR-signalling, epithelial to mesenchymal transition (EMT), and autophagy were analyzed via western blot.

    RESULTS: OR cell lines exhibited increased drug resistance potential compared to H1975. Distinguishable mesenchymal-like features were observed in OR cells. Protein expression analysis revealed EGFR-independent signaling involved in the derived OR cells as well as EMT and autophagy activity.

    CONCLUSION: We generated OR cell lines in-vitro as evidenced by increased drug resistance potential, increased mesenchymal features, and enhanced autophagy activity. Development of Osimertinib resistance cells may serve as in-vitro model facilitating discovery of molecular aberration present during acquired mechanism of resistance.

    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  18. A study on medicinal plants from Malaysia focused on Acalypha siamensis Oliv. ex Gage. isolation and structure of a new tetraterpene, acalyphaser A
    Kambara H, Yamada T, Tsujioka M, Matsunaga S, Tanaka R, Ali HI, et al.
    Chem Biodivers, 2006 Dec;3(12):1301-6.
    PMID: 17193244
    As a part of our chemical studies on Malaysian medicinal plants, five Malaysian plant species were evaluated by cytotoxicity assays using P388 murine leukemia cells. Since Acalypha siamensis exhibited the strongest growth inhibition, its constituents were studied as the object of search for bioactive materials. A novel tetraterpene, acalyphaser A (1), was isolated in the course of the purification. Its structure was elucidated on the basis of 1D- and 2D-NMR techniques, and mass spectrometry.
    Matched MeSH terms: Antineoplastic Agents/pharmacology
  19. Fulltext Nutlin-3, A p53-Mdm2 antagonist for nasopharyngeal carcinoma treatment
    Voon YL, Wong PF, Khoo ASB
    Mini Rev Med Chem, 2018;18(2):173-183.
    PMID: 28714398 DOI: 10.2174/1389557517666170717125821
    Nasopharyngeal carcinoma (NPC) is a form of head and neck cancer of multifactorial etiologies that is highly prevalent among men in the population of Southern China and Southeast Asia. NPC has claimed many thousands of lives worldwide; but the low awareness of NPC remains a hindrance in early diagnosis and prevention of the disease. NPC is highly responsive to radiotherapy and chemotherapy, but radiocurable NPC is still dependent on concurrent treatment of megavoltage radiotherapy with chemotherapy. Despite a significant reduction in loco-regional and distant metastases, radiotherapy alone has failed to provide a significant improvement in the overall survival rate of NPC, compared to chemotherapy. In addition, chemo-resistance persists as the major challenge in the management of metastatic NPC although the survival rate of advanced metastatic NPC has significantly improved with the administration of chemotherapy adjunctive to radiotherapy. In this regard, targeted molecular therapy could be explored for the discovery of alternative NPC therapies. Nutlin-3, a small molecule inhibitor that specifically targets p53-Mdm2 interaction offers new therapeutic opportunities by enhancing cancer cell growth arrest and apoptosis through the restoration of the p53-mediated tumor suppression pathway while producing minimal cytotoxicity and side effects. This review discusses the potential use of Nutlin-3 as a p53-activating drug and the future directions of its clinical research for NPC treatment.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  20. Fulltext Development and Characterization of Calcium-Alginate Beads of Apigenin: In Vitro Antitumor, Antibacterial, and Antioxidant Activities
    Aldawsari MF, Ahmed MM, Fatima F, Anwer MK, Katakam P, Khan A
    Mar Drugs, 2021 Aug 20;19(8).
    PMID: 34436306 DOI: 10.3390/md19080467
    The objective of this work was to develop sustained-release Ca-alginate beads of apigenin using sodium alginate, a natural polysaccharide. Six batches were prepared by applying the ionotropic gelation technique, wherein calcium chloride was used as a crosslinking agent. The beads were evaluated for particle size, drug loading, percentage yield, and in vitro drug release. Particle size was found to decrease, and drug entrapment efficiency was enhanced with an increase in the polymer concentration. The dissolution study showed sustained drug release from the apigenin-loaded alginate beads with an increase in the polymer proportion. Based on the dissolution profiles, BD6 formulation was optimized and characterized for FTIR, DSC, XRD, and SEM, results of which indicated successful development of apigenin-loaded Ca alginate beads. MTT assay demonstrated a potential anticancer effect against the breast cancer MCF-7 cell lines. The antimicrobial activity exhibited effective inhibition in the bacterial and fungal growth rate. The DPPH measurement revealed that the formulation had substantial antioxidant activity, with EC50 value slightly lowered compared to pure apigenin. A stability study demonstrated that the BD6 was stable with similar (f2) drug release profiles in harsh condition. In conclusion, alginate-based beads could be used for sustaining the drug release of poorly water-soluble apigenin while also improving in vitro antitumor, antimicrobial, and antioxidant activity.
    Matched MeSH terms: Antineoplastic Agents/pharmacology
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