Thymoquinone and Costunolide Induce Apoptosis of Both Proliferative and Doxorubicin-Induced-Senescent Colon and Breast Cancer Cells.

in Integrative cancer therapies by Ali H El-Far, Kavitha Godugu, Ahmed E Noreldin, Amna A Saddiq, Omar A Almaghrabi, Soad K Al Jaouni, Shaker A Mousa

TLDR

  • The study investigates how to get rid of cancer cells that have stopped dividing, called senescent cells. The researchers used thymoquinone (TQ) and costunolide (COS) to try to make these senescent cells die. They found that TQ and COS were effective in making the senescent cells die, and that they were more sensitive to these drugs than their normal cells.

Abstract

Doxorubicin (Dox) induces senescence in numerous cancer cell types, but these senescent cancer cells relapse again if they are not eliminated. On this principle, we investigated the apoptotic effect of thymoquinone (TQ), the active ingredient ofseeds and costunolide (COS), the active ingredient of, on the senescent colon (Sen-HCT116) and senescent breast (Sen-MCF7) cancer cell lines in reference to their corresponding proliferative cells to rapidly eliminate the senescent cancer cells. The senescence markers of Sen-HCT116 and Sen-MCF7 were determined by a significant decrease in bromodeoxyuridine (BrdU) incorporation and significant increases in SA-β-gal, p53, and p21 levels. Then proliferative, Sen-HCT116, and Sen-MCF7 cells were subjected to either TQ (50 µM) or COS (30 µM), the Bcl2-associated X protein (Bax), B-cell lymphoma 2 (Bcl2), caspase 3 mRNA expression and its activity were established. Results revealed that TQ significantly increased the Bax/Bcl2 ratio in HCT116 + Dox5 + TQ, MCF7 + TQ, and MCF7 + Dox5 + TQ compared with their corresponding controls. COS significantly increased the Bax/Bcl2 ratio in HCT116 + Dox5 + TQ and MCF7 + Dox5 + TQ compared with their related controls. Also, TQ and COS were significantly increased caspase 3 activity and cell proliferation of Sen-HCT116 and Sen-MCF7. The data revealed a higher sensitivity of senescent cells to TQ or COS than their corresponding proliferative cells.

Overview

  • The study investigates the apoptotic effect of thymoquinone (TQ) and costunolide (COS) on senescent colon (Sen-HCT116) and senescent breast (Sen-MCF7) cancer cell lines in reference to their corresponding proliferative cells. The study aims to rapidly eliminate senescent cancer cells by inducing apoptosis. The methodology used for the experiment includes determining senescence markers, subjecting proliferative, Sen-HCT116, and Sen-MCF7 cells to either TQ or COS, and establishing Bax/Bcl2 ratio, caspase 3 mRNA expression and its activity, and cell proliferation. The primary objective of the study is to determine the apoptotic effect of TQ and COS on senescent cancer cells and their corresponding proliferative cells.

Comparative Analysis & Findings

  • The study compares the outcomes observed under different experimental conditions or interventions, specifically the apoptotic effect of TQ and COS on senescent cancer cells and their corresponding proliferative cells. The results reveal that TQ and COS significantly increased the Bax/Bcl2 ratio, caspase 3 activity, and cell proliferation of Sen-HCT116 and Sen-MCF7 compared with their corresponding controls. The data also shows a higher sensitivity of senescent cells to TQ or COS than their corresponding proliferative cells.

Implications and Future Directions

  • The study's findings suggest that TQ and COS can effectively induce apoptosis in senescent cancer cells, which could lead to the development of new therapeutic strategies for cancer treatment. Future research could explore the use of TQ and COS in combination with other drugs to enhance their apoptotic effect on senescent cancer cells. Additionally, the study highlights the importance of determining senescence markers in cancer treatment and the potential of using these markers to identify and target senescent cancer cells.
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