Inhibition of cancer cell growth in gemcitabine-resistant pancreatic carcinoma by mangiferin phytochemical involves induction of autophagy, endogenous ROS production, cell cycle disruption, mitochondrial mediated apoptosis and suppression of cancer cell migration and invasion.

Lei Yu, Min Chen, Rui Zhang, Zhaohui Jin
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Abstract

Purpose: Pancreatic cancer causes considerable mortality across the globe and the treatment options for pancreatic cancer are limited. Besides, the development of drug resistance among the pancreatic cancer cells makes it even difficult to manage. In this study the anticancer effects of mangiferin were examined against the Mia-PaCa2 gemcitabine-resistant pancreatic cancer cells.

Materials/methods: Cell proliferation was examined by MTT assay while as apoptosis was detected by fluorescent microscopy and western blot. Effects on cell cycle, reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were evaluated by flow cytometry. The fact that mangiferin induced autophagy was demonstrated by fluorescent microscopy in combination with western blot method.

Results: The results revealed that mangiferin inhibited the growth of the Mia-PaCa2 cells and exhibited an IC50 of 10 µM. Nonetheless, the toxic effects of mangiferin were less on the normal cells. Mangiferin induces apoptosis in the Mia-PaCa2 cells which was associated with enhancement of Bax/Bcl-2 ratio. Further investigations revealed that mangiferin triggered autophagy in the Mia-PaCa2 cells as evident from the elevated expressions of the LC3 II and Beclin-1. The antiproliferative effects of mangiferin were also accompanied by the generation of endogenous ROS and cell cycle arrest. Investigation of the effects of mangiferin on the invasion and migration of the Mia-PaCa2 cells showed that mangiferin suppressed the migration and invasion potential of the Mia-PaCa2 cells.

Conclusions: These findings suggest that mangiferin could be utilised for the development of chemotherapy for pancreatic cancer provided further in depth experiments are carried out along with its toxicological studies.

芒果苷植物化学物质对吉西他滨耐药胰腺癌癌细胞生长的抑制作用涉及诱导自噬、内源性 ROS 生成、细胞周期破坏、线粒体介导的细胞凋亡以及抑制癌细胞迁移和侵袭。
目的:胰腺癌在全球造成的死亡率相当高,而胰腺癌的治疗方法却很有限。此外,胰腺癌细胞耐药性的产生使其更加难以控制。本研究考察了芒果苷对 Mia-PaCa2 吉西他滨耐药胰腺癌细胞的抗癌作用:材料/方法: 细胞增殖由 MTT 法检测,细胞凋亡由荧光显微镜和 Western 印迹法检测。流式细胞术评估了芒果苷对细胞周期、活性氧(ROS)生成和线粒体膜电位(MMP)的影响。荧光显微镜结合 Western 印迹法证明了芒果苷诱导自噬的事实:结果表明,芒果苷能抑制 Mia-PaCa2 细胞的生长,其 IC50 值为 10 µM。然而,芒果苷对正常细胞的毒性作用较小。芒果苷能诱导 Mia-PaCa2 细胞凋亡,这与 Bax/Bcl-2 比率的提高有关。进一步研究发现,从 LC3 II 和 Beclin-1 表达的升高可以看出,芒果苷能引发 Mia-PaCa2 细胞的自噬。芒果苷的抗增殖作用还伴随着内源性 ROS 的产生和细胞周期的停滞。芒果苷对Mia-PaCa2细胞侵袭和迁移影响的研究表明,芒果苷抑制了Mia-PaCa2细胞的迁移和侵袭潜力:这些研究结果表明,只要进一步开展深入实验和毒理学研究,芒果苷可用于开发胰腺癌化疗药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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