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Thymoquinone and Costunolide Induce Apoptosis of Both Proliferative and Doxorubicin-Induced-Senescent Colon and Breast Cancer Cells
Integrative Cancer Therapies ( IF 2.9 ) Pub Date : 2021-09-07 , DOI: 10.1177/15347354211035450
Ali H El-Far 1 , Kavitha Godugu 2 , Ahmed E Noreldin 1 , Amna A Saddiq 3 , Omar A Almaghrabi 3 , Soad K Al Jaouni 4 , Shaker A Mousa 2
Affiliation  

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 of Nigella sativa seeds and costunolide (COS), the active ingredient of Costus speciosus, 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.



中文翻译:

百里醌和木香内酯诱导增殖性和阿霉素诱导的衰老结肠癌和乳腺癌细胞的凋亡

多柔比星 (Dox) 可诱导多种癌细胞类型的衰老,但这些衰老的癌细胞如果不被消除,则会再次复发。在此原则下,我们研究了百里醌的凋亡作用(TQ),活性成分果黑种草种子和木香(COS)的活性成分闭鞘姜speciosus, 对衰老结肠 (Sen-HCT116) 和衰老乳腺癌 (Sen-MCF7) 癌细胞系参照其相应的增殖细胞快速清除衰老癌细胞。Sen-HCT116 和 Sen-MCF7 的衰老标志物是通过溴脱氧尿苷 (BrdU) 掺入的显着减少和 SA-β-gal、p53 和 p21 水平的显着增加来确定的。然后对增殖性、Sen-HCT116 和 Sen-MCF7 细胞进行 TQ (50 µM) 或 COS (30 µM)、Bcl2 相关 X 蛋白 (Bax)、B 细胞淋巴瘤 2 (Bcl2)、caspase 3 mRNA表达及其活性被确定。结果显示,与相应的对照相比,TQ 显着增加了 HCT116 + Dox5 + TQ、MCF7 + TQ 和 MCF7 + Dox5 + TQ 中的 Bax/Bcl2 比率。与其相关对照相比,COS 显着增加了 HCT116 + Dox5 + TQ 和 MCF7 + Dox5 + TQ 中的 Bax/Bcl2 比率。此外,TQ 和 COS 显着增加了 Sen-HCT116 和 Sen-MCF7 的半胱天冬酶 3 活性和细胞增殖。数据显示,与相应的增殖细胞相比,衰老细胞对 TQ 或 COS 的敏感性更高。

更新日期:2021-09-07
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