Cytotoxic Activity, Apoptosis Induction and Cell Cycle Arrest in Human Breast Cancer (MCF7) Cells by a Novel Fluorinated Tetrahydro-[1,2,4]Triazolo[3,4-a]Isoquinolin Chalcones

Abstract A series of halogenated chalcones (3–8) was synthesized and confirmed by several spectral tools. The cytotoxic effect of this series was tested against a panel of different cancer cell lines (MCF7, A549, HCT116, and PC3). Our MTT assay results revealed that chalcone 8 had the potent cytotoxic activity against all tested cancer cell lines except A549 cells, which were more sensitive to chalcone 7 relative to the positive control treated with doxorubicin. Chalcone 8 showed the least cytotoxic activity against the normal epithelial cell line RPE-1 and the lowest IC50 at 10.96 µM relative to the IC50 of the chemotherapeutic drug doxorubicin at 12.8 µM against the human breast cancer cell line MCF7. Molecular docking studies showed a good interaction of chalcone 8 with the active site of histone demethylase (PLU-1/ JARID1B) and Carboxy-terminal binding protein1 (CtBP1) proteins. Mechanistically, chalcone 8 induced cell cycle arrest at G2/M phase and apoptosis as assessed by flow cytometry, as well as DNA fragmentation in MCF7 cells. Chalcone 8 upregulated mRNA expression levels of the apoptotic genes BAX, p53, and Caspase-7, Caspase-8, and Caspase-9, whereas mRNA expression levels of the antiapoptotic gene Bcl2, metastasis-related gene matrix metalloproteinase 1, and the autophagic markers ATG5 and LC3B were downregulated as quantified by qPCR.

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Molecular Mechanisms of Thymoquinone as Anticancer agent

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323999201027225305 ◽

2020 ◽

Vol 23 ◽

Author(s):

Fatma Ismail Alhmied ◽

Ali Hassan Alammar ◽

Bayan Mohammed Alsultan ◽

Marooj Alshehri ◽

Faheem Hyder Pottoo

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Human Breast Cancer ◽

Phase Cell ◽

Cycle Phase ◽

Human Breast ◽

Cycle Arrest ◽

Phase Arrest ◽

Anti Cancer

Abstract:: Thymoquinone (TQ), the bioactive constituent of Nigella Sativa seeds is a well-known natural compound for the management of several types of cancers. The anti-cancer properties of thymoquinone are thought to be operated via intervening with various oncogenic pathways including cell cycle arrest, prevention of inflammation and oxidative stress, induction of invasion, metastasis, inhibition of angiogenesis, and apoptosis. As well as up-regulation and down-regulation of specific tumor suppressor genes and tumor promoting genes, respectively. Proliferation of various tumor cells is inhibited by TQ via induction of cell cycle arrest, disruption of the microtubule organization, and down regulating cell survival protein expression. TQ induces G1 phase cell cycle arrest in human breast cancer, colon cancer and osteosarcoma cells through inhibiting the activation of cyclin E or cyclin D and up-regulating p27and p21 a cyclin dependent kinase (Cdk) inhibitor. TQ concentration is a significant factor in targeting a particular cell cycle phase. While high concentration of TQ induced G2 phase arrest in human breast cancer (MCF-7) cells, low concentration causes S phase arrest. This review article provides mechanistic insights into the anti-cancer properties of thymoquinone.

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