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(印度苦瓜和中国苦瓜)提取物通过活性氧介导的线粒体损伤诱导人肺癌细胞系A549凋亡

(Indian and Chinese Bitter Melon) Extracts Inducing Apoptosis in Human Lung Cancer Cell Line A549 via ROS-Mediated Mitochodria Injury.

作者信息

Thiagarajan Siroshini, Arapoc Daryl J, Husna Shafie Nurul, Keong Yong Yoke, Bahari Hasnah, Adam Zainah, Ei Thandar

机构信息

Department of Human Anatomy, Faculty of Medicine and Health Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.

Malaysian Nuclear Agency, 43000 Kajang, Selangor, Malaysia.

出版信息

Evid Based Complement Alternat Med. 2019 Mar 6;2019:2821597. doi: 10.1155/2019/2821597. eCollection 2019.

Abstract

Lung cancer is the leading cause of cancer related deaths worldwide with about 40% occurring in developing countries. The two varieties of , which are Chinese and Indian bitter melon, have been subjected to antiproliferative activity in human non-small cell lung cells A549. The A549 cells were treated with hot and cold aqueous extraction for both the bitter melon varieties, and the antiproliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptotic mechanism of action on A549 human lung cancer cells was evaluated first morphologically using Hoechst 33358, and cytoskeleton staining using Filamentous-actin (F-actin) cytoskeleton FICT and DAPI followed by caspase-3/7, reactive oxygen species (ROS), and p53 activity. Chinese hot aqueous extraction (CHA) exhibited potent antiproliferative activity against A549 human lung cancer cells. The morphological analysis of mitochondria destruction and the derangement of cytoskeleton showed apoptosis-inducing activity. CHA increased the caspase-3/7 activity by 1.6-fold and the ROS activity by 5-fold. Flow cytometric analysis revealed 34.5% of apoptotic cells significantly (p<0.05) compared to cisplatin-treated A549 human cancer cells. CHA is suggested to induce apoptosis due to their rich bioactive chemical constituents. These findings suggest that the antiproliferative effect of CHA was due to apoptosis via ROS-mediated mitochondria injury.

摘要

肺癌是全球癌症相关死亡的主要原因,约40%的病例发生在发展中国家。两种苦瓜品种,即中国苦瓜和印度苦瓜,已在人非小细胞肺癌细胞A549中进行了抗增殖活性研究。对这两种苦瓜品种的细胞分别进行热和冷的水提取处理,并通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法评估其抗增殖活性。首先使用Hoechst 33358对A549人肺癌细胞的凋亡作用机制进行形态学评估,然后使用丝状肌动蛋白(F-肌动蛋白)细胞骨架荧光免疫细胞化学技术(FICT)和4',6-二脒基-2-苯基吲哚(DAPI)进行细胞骨架染色,随后检测半胱天冬酶-3/7、活性氧(ROS)和p53活性。中国苦瓜热水提取物(CHA)对A549人肺癌细胞表现出强大的抗增殖活性。线粒体破坏和细胞骨架紊乱的形态学分析显示其具有诱导凋亡的活性。CHA使半胱天冬酶-3/7活性增加了1.6倍,ROS活性增加了5倍。流式细胞术分析显示,与顺铂处理的A549人癌细胞相比,CHA处理的细胞中有34.5%的细胞发生凋亡,差异具有统计学意义(p<0.05)。由于CHA富含生物活性化学成分,提示其可诱导细胞凋亡。这些发现表明,CHA的抗增殖作用是通过ROS介导的线粒体损伤导致细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/141e/6431397/6a0622f72226/ECAM2019-2821597.001.jpg

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