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  1. 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: Cell Proliferation/drug effects
  2. Wang Y, Gao F, Ooi KK, Tai Q, Zhang J, Zhu Y, et al.
    J Environ Pathol Toxicol Oncol, 2019;38(4):297-311.
    PMID: 32464002 DOI: 10.1615/JEnvironPatholToxicolOncol.2019030482
    Early development of liver cancer is usually asymptomatic. The overall survival rate of patients is relatively low due to late diagnosis, despite hepatocellular carcinoma being a common diagnosis. The high mortality rate of liver cancer was due to its overactivated cellular mitochondrial activities, namely thioredoxin reductase enzymatic activities and its downstream activation of nuclear factor kappa B (NF-κB) signaling pathways for cancer cell migration. Our previous study on this candidate compound on A2780 ovarian cancer cells and MCF-7 breast cancer cells, through modulation of cell-cycle checkpoints and respective targeted apoptosis pathways. The current study used HepG2 hepatocellular carcinoma cell lines as a representative in vitro liver cancer cell model. The half maximal inhibitory concentration (IC50) value was obtained via incubation of PTZ compound for 24 h yield of 37.03 μM, whereby it was three-fold more potent than the standard control tested, cisplatin (109.23 μM). The subsequent application of IC50 dosage of PTZ onto HepG2 cells illustrated a growth-static effect via activation of S-phase cell-cycle checkpoints, immediately followed by regulation of apoptosis. Increased cellular concentration of reactive oxygen species eventually generated oxidative damages on mitochondria, hence resulting in the release of cytochrome c protein and suppression of TrxR enzymatic activity, in conjunction with the suppression on invasion of cancer cells via Matrigel invasion chamber. In conclusion, PTZ was hypothesized to act effectively on mitochondria of HepG2 cells; hence it should proceed into detailed drug targeting mechanism research.
    Matched MeSH terms: Cell Proliferation/drug effects
  3. Tahlan S, Narasimhan B, Lim SM, Ramasamy K, Mani V, Shah SAA
    Mini Rev Med Chem, 2019;19(13):1080-1092.
    PMID: 30306865 DOI: 10.2174/1389557518666181009151008
    BACKGROUND: Increased rate of mortality due to the development of resistance to currently available antimicrobial and anticancer agents initiated the need to develop new chemical entities for the treatment of microbial infections and cancer.

    OBJECTIVE: The present study was aimed to synthesize and evaluate antimicrobial and anticancer activities of Schiff bases of 2-mercaptobenzimidazole.

    METHODS: The Schiff bases of 2-mercaptobenzimidazole were synthesized from 4-(2-(1H-benzo[d]- imidazol-2-ylthio)acetamido)benzohydrazide. The synthesized compounds were evaluated for antimicrobial and anticancer activities by tube dilution method and Sulforhodamine-B (SRB) assay, respectively.

    RESULTS: Compounds 8 (MICpa, an = 2.41, 1.20 µM/ml), 10 (MICse, sa = 2.50 µM/ml), 20 (MICec = 2.34 µM/ml) and 25 (MICca = 1.46 µM/ml) showed significant antimicrobial activity against tested bacterial and fungal strains and compounds 20 (IC50 = 8 µg/ml) and 23 (IC50 = 7 µg/ml) exhibited significant anticancer activity.

    CONCLUSION: In general, the synthesized derivatives exhibited moderate antimicrobial and anticancer activities. Compounds 8 and 25 having high antifungal potential among the synthesized compounds may be taken as lead molecules for the development of novel antifungal agents.

    Matched MeSH terms: Cell Proliferation/drug effects
  4. Abu N, Akhtar MN, Ho WY, Yeap SK, Alitheen NB
    Molecules, 2013 Aug 27;18(9):10367-77.
    PMID: 23985955 DOI: 10.3390/molecules180910367
    Breast cancer is becoming more prominent in women today. As of now, there are no effective treatments in treating metastatic breast cancer. We have tested the cytotoxic and anti-migration effects of BHAQ, a synthesized anthraquinone, on two breast cancer cell lines, MCF-7 and MDA-MB231. Anthraquinones are an interesting class of molecules that display a wide spectrum of biological applications, including anticancer properties. Cellular inhibition was tested through a MTT assay, double acridine orange/propidium iodide staining and FACS cell cycle analysis. Inhibition of migration was tested by the wound healing method, and migration through a Boyden chamber. BHAQ was cytotoxic towards both cell lines in a dose dependent and possibly cell-dependent manner. Additionally, BHAQ also inhibited the migration of the highly metastatic MDA-MB231 cell line.
    Matched MeSH terms: Cell Proliferation/drug effects
  5. Touri M, Moztarzadeh F, Osman NAA, Dehghan MM, Mozafari M
    Mater Sci Eng C Mater Biol Appl, 2018 Mar 01;84:236-242.
    PMID: 29519434 DOI: 10.1016/j.msec.2017.11.037
    Tissue engineering scaffolds with oxygen generating elements have shown to be able to increase the level of oxygen and cell survivability in specific conditions. In this study, biphasic calcium phosphate (BCP) scaffolds with the composition of 60% hydroxyapatite (HA) and 40% beta-tricalcium phosphate (β-TCP), which have shown a great potential for bone tissue engineering applications, were fabricated by a direct-write assembly (robocasting) technique. Then, the three-dimensional (3D)-printed scaffolds were coated with different ratios of an oxygen releasing agent, calcium peroxide (CPO), which encapsulated within a polycaprolactone (PCL) matrix through dip-coating, and used for in situ production of oxygen in the implanted sites. The structure, composition and morphology of the prepared scaffolds were characterized by different techniques. The oxygen release kinetics and biological investigations of the scaffolds were also studied in vitro. The results showed that oxygen release behaviour was sustained and dependant on the concentration of CPO encapsulated in the PCL coating matrix. It was also demonstrated that the coated scaffolds, having 3% CPO in the coating system, could provide a great potential for promoting bone ingrowth with improving osteoblast cells viability and proliferation under hypoxic conditions. The findings indicated that the prepared scaffolds could play a significant role in engineering of large bone tissue implants with limitations in oxygen diffusion.
    Matched MeSH terms: Cell Proliferation/drug effects
  6. Yuandani, Jantan I, Husain K
    BMC Complement Altern Med, 2017 Apr 11;17(1):211.
    PMID: 28399868 DOI: 10.1186/s12906-017-1726-z
    BACKGROUND: Gynura segetum is used traditionally to treat various ailments related to the immune system, which include cancer, inflammation, rheumatism, diabetes, hypertension, and viral infections but little studies have been carried out to validate their ethnopharmacological aspects. In this study the immunosuppressive effects of G. segetum and its constituents were investigated.

    METHODS: Isolation of compounds from G. segetum leaves was conducted using vacuum liquid chromatography (VLC) and column chromatography (CC). Two new compounds, namely 4,5,4'-trihydroxychalcone and 8,8'-(ethene-1,2-diyl)-dinaphtalene-1,4,5-triol, together with stigmasterol and β-sitosterol were isolated from G. segetum methanol extract and their structures were determined spectroscopically. The presence of gallic acid and rutin in the extract was determined quantitatively by a validated HPLC method. G. segetum methanol extract and its constituents were investigated for their effects on chemotaxis, phagocytosis, β2 integrin (CD18) expression, and reactive oxygen species (ROS) of polymorphonuclear leukocytes (PMNs), lymphocytes proliferation, cytokine release and nitric oxide (NO) production of phagocytes.

    RESULTS: All the samples significantly inhibited all the innate immune responses tested except CD 18 expression on surface of leukocytes. Among the samples, 8,8'-(ethene-1,2-diyl)-dinaphtalene-1,4,5-triol exhibited the strongest inhibitory on chemotaxis, phagocytosis, ROS and NO production. The compound exhibited exceptionally strong inhibitions on ROS and chemotaxis activities with IC50 values lower than the positive controls, aspirin and ibuprofen, respectively. 4,5,4'-Trihydroxychalcone revealed the strongest immunosuppressive activity on proliferation of lymphocytes (IC50 value of 1.52 μM) and on release of IL-1β (IC50 value of 6.69 μM). Meanwhile rutin was the most potent sample against release of TNF-α from monocytes (IC50, 16.96 μM).

    CONCLUSION: The extract showed strong immunosuppressive effects on various components of the immune system and these activities were possibly contributed mainly by 4,5,4'-trihydroxychalcone, 8,8'-(ethene-1,2-diyl)-dinaphtalene-1,4,5-triol and rutin.

    Matched MeSH terms: Cell Proliferation/drug effects
  7. Tan BS, Kang O, Mai CW, Tiong KH, Khoo AS, Pichika MR, et al.
    Cancer Lett, 2013 Aug 9;336(1):127-39.
    PMID: 23612072 DOI: 10.1016/j.canlet.2013.04.014
    6-Shogaol has been shown to possess many antitumor properties including inhibition of cancer cell growth, inhibition of cancer metastasis, induction of apoptosis in cancer cells and induction of cancer cell differentiation. Despite its prominent antitumor effects, the direct molecular target of 6-shogaol has remained elusive. To identify the direct targets of 6-shogaol, a comprehensive antitumor profile of 6-shogaol (NSC752389) was tested in the NCI-60 cell line in an in vitro screen. The results show that 6-shogaol is COMPARE negative suggesting that it functions via a mechanism of action distinct from existing classes of therapeutic agents. Further analysis using microarray gene profiling and Connectivity Map analysis showed that MCF-7 cells treated with 6-shogaol display gene expression signatures characteristic of peroxisome proliferator activated receptor γ (PPARγ) agonists, suggesting that 6-shogaol may activate the PPARγ signaling pathway for its antitumor effects. Indeed, treatment of MCF-7 and HT29 cells with 6-shogaol induced PPARγ transcriptional activity, suppressed NFκB activity, and induced apoptosis in breast and colon cancer cells in a PPARγ-dependent manner. Furthermore, 6-shogaol is capable of binding to PPARγ with a binding affinity comparable to 15-delta prostaglandin J2, a natural ligand for PPARγ. Together, our findings suggest that the antitumor effects of 6-shogaol are mediated through activation of PPARγ and imply that activation of PPARγ might be beneficial for breast and colon cancer treatment.
    Matched MeSH terms: Cell Proliferation/drug effects*
  8. 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: Cell Proliferation/drug effects
  9. Hajrezaie M, Paydar M, Moghadamtousi SZ, Hassandarvish P, Gwaram NS, Zahedifard M, et al.
    ScientificWorldJournal, 2014;2014:540463.
    PMID: 24737979 DOI: 10.1155/2014/540463
    Metal-based drugs with extensive clinical applications hold great promise for the development of cancer chemotherapeutic agents. In the last few decades, Schiff bases and their complexes have become well known for their extensive biological potential. In the present study, we examined the antiproliferative effect of a copper (II) complex on HT-29 colon cancer cells. The Cu(BrHAP)2 Schiff base compound demonstrated a potent antiproliferative effect in HT-29 cells, with an IC50 value of 2.87  μg/ml after 72 h of treatment. HT-29 cells treated with Cu (II) complexes underwent apoptosis death, as exhibited by a progressive elevation in the proportion of the G1 cell population. At a concentration of 6.25  μg/ml, the Cu(BrHAP)2 compound caused significant elevation in ROS production following perturbation of mitochondrial membrane potential and cytochrome c release, as assessed by the measurement of fluorescence intensity in stained cells. Furthermore, the activation of caspases 3/7 and 9 was part of the Cu (II) complex-induced apoptosis, which confirmed the involvement of mitochondrial-mediated apoptosis. Meanwhile, there was no significant activation of caspase-8. Taken together, these results imply that the Cu(BrHAP)2 compound is a potential candidate for further in vivo and clinical colon cancer studies to develop novel chemotherapeutic agents derived from metal-based agents.
    Matched MeSH terms: Cell Proliferation/drug effects
  10. Boukari Y, Qutachi O, Scurr DJ, Morris AP, Doughty SW, Billa N
    J Biomater Sci Polym Ed, 2017 Nov;28(16):1966-1983.
    PMID: 28777694 DOI: 10.1080/09205063.2017.1364100
    The development of patient-friendly alternatives to bone-graft procedures is the driving force for new frontiers in bone tissue engineering. Poly (dl-lactic-co-glycolic acid) (PLGA) and chitosan are well-studied and easy-to-process polymers from which scaffolds can be fabricated. In this study, a novel dual-application scaffold system was formulated from porous PLGA and protein-loaded PLGA/chitosan microspheres. Physicochemical and in vitro protein release attributes were established. The therapeutic relevance, cytocompatibility with primary human mesenchymal stem cells (hMSCs) and osteogenic properties were tested. There was a significant reduction in burst release from the composite PLGA/chitosan microspheres compared with PLGA alone. Scaffolds sintered from porous microspheres at 37 °C were significantly stronger than the PLGA control, with compressive strengths of 0.846 ± 0.272 MPa and 0.406 ± 0.265 MPa, respectively (p cell numbers observed over an 8-day study period. Von Kossa and immunostaining of the hMSC-scaffolds confirmed their osteogenic potential with the ability to sinter at 37 °C in situ.
    Matched MeSH terms: Cell Proliferation/drug effects
  11. Bharkavi C, Vivek Kumar S, Ashraf Ali M, Osman H, Muthusubramanian S, Perumal S
    Bioorg Med Chem, 2016 11 15;24(22):5873-5883.
    PMID: 27687968 DOI: 10.1016/j.bmc.2016.09.044
    A facile stereoselective synthesis of novel dispiro indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids has been achieved by 1,3-dipolar cycloaddition of azomethine ylides, generated in situ from ninhydrin and sarcosine/thiaproline, on a series of 3-benzylidenethiochroman-4-ones. The synthesised compounds were screened for their antimycobacterial, anticancer and AchE inhibition activities. Compound 4l (IC50 1.07μM) has been found to exhibit the most potent antimycobacterial activity compared to cycloserine (12 times), pyrimethamine (37 times) and ethambutol (IC50 <1.56μM) and 6l (IC50=2.87μM) is more active than both cycloserine (4 times) and pyrimethamine (12 times). Three compounds, 4a, 6b and 6i, display good anticancer activity against CCRF-CEM cell lines. Compounds 6g and 4g display maximum AchE inhibitory activity with IC50 values of 1.10 and 1.16μmol/L respectively.
    Matched MeSH terms: Cell Proliferation/drug effects
  12. Shu YH, Yuan HH, Xu MT, Hong YT, Gao CC, Wu ZP, et al.
    Acta Pharmacol Sin, 2021 May;42(5):780-790.
    PMID: 32814819 DOI: 10.1038/s41401-020-0492-5
    Guangsangon E (GSE) is a novel Diels-Alder adduct isolated from leaves of Morus alba L, a traditional Chinese medicine widely applied in respiratory diseases. It is reported that GSE has cytotoxic effect on cancer cells. In our research, we investigated its anticancer effect on respiratory cancer and revealed that GSE induces autophagy and apoptosis in lung and nasopharyngeal cancer cells. We first observed that GSE inhibits cell proliferation and induces apoptosis in A549 and CNE1 cells. Meanwhile, the upregulation of autophagosome marker LC3 and increased formation of GFP-LC3 puncta demonstrates the induction of autophagy in GSE-treated cells. Moreover, GSE increases the autophagy flux by enhancing lysosomal activity and the fusion of autophagosomes and lysosomes. Next, we investigated that endoplasmic reticulum (ER) stress is involved in autophagy induction by GSE. GSE activates the ER stress through reactive oxygen species (ROS) accumulation, which can be blocked by ROS scavenger NAC. Finally, inhibition of autophagy attenuates GSE-caused cell death, termed as "autophagy-mediated cell death." Taken together, we revealed the molecular mechanism of GSE against respiratory cancer, which demonstrates great potential of GSE in the treatment of representative cancer.
    Matched MeSH terms: Cell Proliferation/drug effects
  13. Dai X, Wang L, Deivasigamni A, Looi CY, Karthikeyan C, Trivedi P, et al.
    Oncotarget, 2017 Feb 21;8(8):12831-12842.
    PMID: 28086233 DOI: 10.18632/oncotarget.14606
    A prior screening programme carried out using MTT assay by our group identified a series of novel benzimidazole derivatives, among which Methyl 2-(5-fluoro-2-hydroxyphenyl)-1H- benzo[d]imidazole-5-carboxylate (MBIC) showed highest anticancer efficacy compared to that of chemotherapeutic agent, cisplatin. In the present study, we found that MBIC inhibited cell viability in different hepatocellular carcinoma (HCC) cell lines without exerting significant cytotoxic effects on normal liver cells. Annexin V-FITC/PI flow cytometry analysis and Western blotting results indicated that MBIC can induce apoptosis in HCC cells, which was found to be mediated through mitochondria associated proteins ultimately leading to the activation of caspase-3. The exposure to MBIC also resulted in remarkable impairment of HCC cell migration and invasion. In addition, treatment with MBIC led to a rapid generation of reactive oxygen species (ROS) and substantial activation of c-Jun-N-terminal kinase (JNK). The depletion of ROS by N-Acetyl cysteine (NAC) partially blocked MBIC-induced apoptosis and JNK activation in HCC cells. Finally, MBIC significantly inhibited tumor growth at a dose of 25 mg/kg in an orthotopic HCC mouse model. Taken together, these results demonstrate that MBIC may inhibit cell proliferation via ROS-mediated activation of the JNK signaling cascade in HCC cells.
    Matched MeSH terms: Cell Proliferation/drug effects
  14. Ghalib RM, Hashim R, Sulaiman O, Mehdi SH, Valkonen A, Rissanen K, et al.
    Eur J Med Chem, 2012 Jan;47(1):601-7.
    PMID: 22074984 DOI: 10.1016/j.ejmech.2011.10.037
    In this study the novel caryophyllene type sesquiterpene lactone (aspfalcolide) has been isolated from the leaves of Asparagus falcatus (Linn.) and characterized by IR, 1D NMR, 2D NMR, EI-MS, HR-ESI-MS and X-ray single crystal diffraction analysis. The aspfalcolide crystallizes in the orthorhombic space group P2(1)2(1)2(1) with a = 6.37360(10), b = 7.6890(2), c = 27.3281(6) Å, α = β = γ = 90(°) and Z = 4. One intermolecular O-H⋯O hydrogen bond enforces these natural molecules to form infinite chains through the crystal. Aspfalcolide was screened for its anti-angiogenic activity in human umbilical vein endothelial cells (HUVECs) and the result showed the remarkable inhibitory effect of aspfalcolide on the proliferation (IC(50) 1.82 μM), migration and tube formation of HUVECs.
    Matched MeSH terms: Cell Proliferation/drug effects
  15. Jaganathan SK, Balaji A, Vellayappan MV, Asokan MK, Subramanian AP, John AA, et al.
    Anticancer Agents Med Chem, 2015;15(1):48-56.
    PMID: 25052987
    Recent statistics revealed that cancer is one among the main reasons for death throughout the world. Several treatments are available but still there is no cure when it is detected at late stages. One of the treatment modes for cancer is chemotherapy which utilizes anticancer drugs in order to eradicate the cancer cells by apoptosis. Apoptosis is a programmed cell death through which body maintains homeostasis or kills cancer cells by utilizing its cell machinery. Recent researches have concluded that dietary agents have a putative role in instituting apoptosis of cancer cells. Honey, one of the victuals rich in antioxidants, has a long-standing exposure to humans and its role in cancer prevention and treatment is a topic of current interest. Various researchers have been experimenting honey against different cancers and provided valuable insights about the apoptosis induced by the honey. This review will highlight the recent findings of apoptotic mechanism involved in different cancer cells. Further it also reports antitumor activity of honey in some animal models. Hence it is high-time to initiate more preclinical trials as well as clinical experiments which would further add to the knowledge of anticancer nature of honey and also endorse honey as a potential candidate in the war against cancer.
    Matched MeSH terms: Cell Proliferation/drug effects*
  16. Gill MR, Harun SN, Halder S, Boghozian RA, Ramadan K, Ahmad H, et al.
    Sci Rep, 2016 08 25;6:31973.
    PMID: 27558808 DOI: 10.1038/srep31973
    Ruthenium(II) polypyridyl complexes can intercalate DNA with high affinity and prevent cell proliferation; however, the direct impact of ruthenium-based intercalation on cellular DNA replication remains unknown. Here we show the multi-intercalator [Ru(dppz)2(PIP)](2+) (dppz = dipyridophenazine, PIP = 2-(phenyl)imidazo[4,5-f][1,10]phenanthroline) immediately stalls replication fork progression in HeLa human cervical cancer cells. In response to this replication blockade, the DNA damage response (DDR) cell signalling network is activated, with checkpoint kinase 1 (Chk1) activation indicating prolonged replication-associated DNA damage, and cell proliferation is inhibited by G1-S cell-cycle arrest. Co-incubation with a Chk1 inhibitor achieves synergistic apoptosis in cancer cells, with a significant increase in phospho(Ser139) histone H2AX (γ-H2AX) levels and foci indicating increased conversion of stalled replication forks to double-strand breaks (DSBs). Normal human epithelial cells remain unaffected by this concurrent treatment. Furthermore, pre-treatment of HeLa cells with [Ru(dppz)2(PIP)](2+) before external beam ionising radiation results in a supra-additive decrease in cell survival accompanied by increased γ-H2AX expression, indicating the compound functions as a radiosensitizer. Together, these results indicate ruthenium-based intercalation can block replication fork progression and demonstrate how these DNA-binding agents may be combined with DDR inhibitors or ionising radiation to achieve more efficient cancer cell killing.
    Matched MeSH terms: Cell Proliferation/drug effects
  17. Kanagasabapathy G, Chua KH, Malek SN, Vikineswary S, Kuppusamy UR
    Food Chem, 2014 Feb 15;145:198-204.
    PMID: 24128468 DOI: 10.1016/j.foodchem.2013.08.051
    Mushrooms have been used to treat various diseases for thousands of years. In the present study, the effects of Pleurotus sajor-caju mushroom on lipogenesis, lipolysis and oxidative stress in 3T3-L1 cells were investigated. The β-glucan-rich polysaccharides (GE) from P. sajor-caju stimulated lipogenesis and lipolysis but attenuated protein carbonyl and lipid hydroperoxide levels in 3T3-L1 cells. This extract caused an increase in the expression of 5'-AMP-activated protein kinase subunit γ-2 (PKRAG2) and 5'-AMP-activated protein kinase subunit γ-3 (PKRAG3) when compared to control (untreated) cells. Moreover, GE induced the expressions of hormone-sensitive lipase, adipose triglyceride lipase enzymes, leptin, adiponectin and glucose transporter-4 in 3T3-L1 cells which may have contributed to the lipolytic and insulin-like activities observed in this study. These findings suggest that GE is a novel AMPK activator that may be valuable in the formulation of nutraceuticals and functional food for the prevention and treatment of diabetes mellitus.
    Matched MeSH terms: Cell Proliferation/drug effects
  18. Lim SW, Ting KN, Bradshaw TD, Zeenathul NA, Wiart C, Khoo TJ, et al.
    J Ethnopharmacol, 2011 Nov 18;138(2):616-23.
    PMID: 22008878 DOI: 10.1016/j.jep.2011.10.005
    The seeds of Acalypha wilkesiana have been used empirically by traditional healers in Southwest Nigeria together with other plants as a powder mixture to treat patients with breast tumours and inflammation.
    Matched MeSH terms: Cell Proliferation/drug effects
  19. Arulnathan SB, Leong KH, Ariffin A, Kareem HS, Cheah KKH
    Anticancer Agents Med Chem, 2020;20(9):1072-1086.
    PMID: 32188392 DOI: 10.2174/1871520620666200318100051
    BACKGROUND: Oxadiazoles, triazoles, and their respective precursors have been shown to exhibit various pharmacological properties, namely antitumour activities. Cytotoxic activity was reported for these compounds in various cancer cell lines.

    AIM AND OBJECTIVES: In this study, we aim at investigating the mechanism of apoptosis by N-(4-chlorophenyl)-2-(4- (3,4,5-trimethoxybenzyloxy)benzoyl)-hydrazinecarbothioamide, a triazole precursor, henceforth termed compound P7a, in breast cancer cell line, MCF-7. We first screen a series of analogues containing (3,4,5-trimethoxybenzyloxy) phenyl moiety in breast cancer cell lines (MCF-7 and MDA-MB-231) to select the most cytotoxic compound and demonstrate a dose- and time-dependent cytotoxicity. Then, we unravel the mechanism of apoptosis of P7a in MCF-7 as well as its ability to cause cell cycle arrest.

    METHODS: Synthesis was performed as previously described by Kareem and co-workers. Cytotoxicity of analogues containing (3,4,5-trimethoxybenzyloxy)phenyl moiety against MCF-7 and MDA-MB-231 cell lines was evaluated using the MTS assay. Flow cytometric analyses was done using Annexin V/PI staining, JC-1 staining and ROS assay. The activity of caspases using a chemoluminescence assay and western blot analysis was conducted to study the apoptotic pathway induced by the compound in MCF-7 cells. Lastly, cell cycle analysis was conducted using flow cytometry.

    RESULTS: Upon 48 hours of treatment, compound P7a inhibited the proliferation of human breast cancer cells with IC50 values of 178.92 ± 12.51μM and 33.75 ± 1.20μM for MDA-MB-231 and MCF-7, respectively. Additionally, compound P7a showed selectivity towards the cancer cell line, MCF-7 compared to the normal breast cell line, hTERT-HME1, an advantage against current anticancer drugs (tamoxifen and vinblastine). Flow cytometric analyses using different assays indicated that compound P7a significantly increased the proportion of apoptotic cells, increased mitochondria membrane permeabilisation and caused generation of ROS in MCF-7. In addition, cell cycle analysis showed that cell proliferation was arrested at the G1 phase in the MCF-7 cell line. Furthermore, upon treatment, the MCF-7 cell line showed increased activity of caspase-3/7, and caspase-9. Lastly, the western blot analysis showed the up-regulation of pro-apoptotic proteins along with up-regulation of caspase-7 and caspase-9, indicating that an intrinsic pathway of apoptosis was induced.

    CONCLUSION: The results suggest that compound P7a could be a potential chemotherapeutic agent for breast cancer.

    Matched MeSH terms: Cell Proliferation/drug effects
  20. Ong YS, Saiful Yazan L, Ng WK, Noordin MM, Sapuan S, Foo JB, et al.
    Int J Nanomedicine, 2016 11 09;11:5905-5915.
    PMID: 27877037
    BACKGROUND: Thymoquinone (TQ), the predominant active lipophilic component in Nigella sativa seed oil, has a variety of pharmacological properties such as anticancer activities. However, translation of TQ to clinical phase is still not possible due to its hydrophobic properties. This problem can be solved by encapsulating it in nanoformulations to enhance its pharmacological properties. In our previous study, TQ has been successfully encapsulated in a nanostructured lipid carrier (hereinafter referred to as TQNLC) with excellent physiochemical properties such as high encapsulation efficiency, high drug-loading capacity, particle diameter less than 100 nm, and stability up to 2 years. In vitro studies also proved that TQNLC exhibited antiproliferative activity toward breast and cervical cancer cell lines. However, no toxicity profile related to this formulation has been reported. In this study, we determine and compare the in vivo toxicity of both TQNLC and TQ.

    MATERIALS AND METHODS: The in vivo toxicity (acute and subacute toxicity) study was carried out by oral administration of TQNLC and TQ to BALB/c mice. Animal survival, body weight, organ weight-to-body weight ratio, hematological profile, biochemistry profile, and histopathological changes were analyzed.

    RESULTS: In acute toxicity, TQ that is loaded in nanostructured lipid carrier (NLC) was found to be less toxic than pure TQ. It can be concluded that encapsulation of TQ in lipid carrier minimizes the toxicity of the compound. In the subacute toxicity study, oral administration of 100 mg/kg of TQNLC and TQ did not cause mortality to either male or female but resulted in toxicity to the liver. It is postulated that long-term consumption of TQNLC and TQ may cause toxicity to the liver but not to the extent of altering the functions of the organ. For both treatments, the no observed adverse effect level (NOAEL) was found to be 10 mg/kg/d for mice in both sexes.

    CONCLUSION: For long-term oral consumption, TQ and TQNLC at a dose of 10 mg/kg is safe in mice and does not exert any toxic effect. The results provide safety information of TQNLC, which would further help researchers in clinical use.

    Matched MeSH terms: Cell Proliferation/drug effects
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