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γ-生育三烯酚协同促进依托泊苷对乳腺癌细胞系的抗增殖和促凋亡作用。

Gamma-Tocotrienol Synergistically Promotes the Anti-proliferative and Pro-apoptotic Effects of Etoposide on Breast Cancer Cell Lines.

作者信息

Idriss Maya, Younes Maria, Abou Najem Sonia, Hodroj Mohammad Hassan, Fakhoury Rajaa, Rizk Sandra

机构信息

Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Byblos 36, Lebanon.

Department of Biological Sciences, Faculty of Science, Beirut Arab University, Beirut 11-5020, Lebanon.

出版信息

Curr Mol Pharmacol. 2022;15(7):980-986. doi: 10.2174/1874467215666220131095611.

DOI:10.2174/1874467215666220131095611
PMID:35100963
Abstract

BACKGROUND

Breast Cancer is one of the most commonly diagnosed cancers worldwide and a major cause of death among women. Although chemotherapeutic agents remain the keystones in cancer therapy, significant side effects have failed to provide a safe and tolerable treatment for cancer patients. Dietary antioxidant vitamins were extensively investigated over the past years and their relevance in cancer chemotherapy remains to be elucidated.

OBJECTIVE

In the current study, we aimed to investigate the anti-proliferative and apoptotic effects of combining γ-tocotrienol, a member of the vitamin E family, with the chemotherapeutic drug etoposide in MCF-7 and MDA-MB-231 breast cancer cell lines.

METHODS

The antiproliferative effect of etoposide combined with γ-tocotrienol was measured using MTS viability reagent. The pro-apoptotic effect was elucidated through Cell Death ELISA and dual Annexin V/PI staining followed by flow cytometric analysis.

RESULTS

Our results showed that etoposide significantly decreased the cell growth of both cell lines, with MDA-MB-231 cells being more sensitive to etoposide treatment than MCF-7. Moreover, simultaneous treatment of both breast cancer cell lines with low doses of γ-tocotrienol and etoposide induced a synergistic antiproliferative effect (CI<1). Furthermore, the combination therapy significantly increased the percentage of total apoptotic cells in the MDA-MB-231 cell line and the degree of DNA fragmentation as compared to treatment with either compound alone.

CONCLUSION

In conclusion, our results provide evidence for the profound anti-tumorigenic effect of combined etoposide and γ-tocotrienol in the breast cancer cell lines.

摘要

背景

乳腺癌是全球最常被诊断出的癌症之一,也是女性死亡的主要原因。尽管化疗药物仍是癌症治疗的基石,但严重的副作用使得无法为癌症患者提供安全且可耐受的治疗。过去几年对膳食抗氧化维生素进行了广泛研究,但其在癌症化疗中的相关性仍有待阐明。

目的

在本研究中,我们旨在探讨维生素E家族成员γ-生育三烯酚与化疗药物依托泊苷联合应用于MCF-7和MDA-MB-231乳腺癌细胞系时的抗增殖和凋亡作用。

方法

使用MTS活力试剂测定依托泊苷与γ-生育三烯酚联合应用的抗增殖作用。通过细胞死亡ELISA和双Annexin V/PI染色,随后进行流式细胞术分析来阐明促凋亡作用。

结果

我们的结果表明,依托泊苷显著降低了两种细胞系的细胞生长,MDA-MB-231细胞比MCF-7细胞对依托泊苷治疗更敏感。此外,用低剂量γ-生育三烯酚和依托泊苷同时处理两种乳腺癌细胞系诱导了协同抗增殖作用(CI<1)。此外,与单独使用任一化合物治疗相比,联合治疗显著增加了MDA-MB-231细胞系中总凋亡细胞的百分比和DNA片段化程度。

结论

总之,我们的结果为依托泊苷和γ-生育三烯酚联合应用于乳腺癌细胞系具有深远的抗肿瘤作用提供了证据。

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