Department of Oncology, Shanxi Sengong Hospital, No. 9 Huazhan Street, Hu Xian, Xi'an, 710300, Shanxi Province, China.
Department of Oncology, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
Arch Pharm Res. 2016 Oct;39(10):1441-1453. doi: 10.1007/s12272-016-0815-8. Epub 2016 Sep 6.
Isoalantolactone possessed various biological activities. However, whether it could treat breast cancer and its underlying mechanism remained largely unknown. This study was designed to evaluate the anticancer effects of isoalantolactone on breast cancer and explored the molecular mechanism. Two human breast cancer cell lines (MDA-MB-231 and MCF-7) and one normal breast cell line (MCF-10A) were applied. Our data suggested that isoalantolactone decreased breast cancer cell viability in a dose-dependent manner, but showed almost no toxicity to MCF-10A cells. The anticancer effects of isoalantolactone were related to the overexpression of reactive oxygen species. Isoalantolactone significantly induced breast cancer cell apoptosis by activating caspase cascade, cleaving poly (ADP-ribose) polymerase. Increase of Bax/Bcl-2 ratio, depolarization of mitochondrial membrane potential, release of cytochrome c from mitochondria to cytoplasm and cell cycle arrest at G2/M phase were associated to the apoptosis induction. Additionally, isoalantolactone increased the protein expression of p38 MAPK and JNK. The apoptosis-induction of isoalantolactone could be abrogated by co-treatment with SB203580 (inhibitor of p38 MAPK) or SP600125 (inhibitor of JNK). Furthermore, isoalantolactone induced breast cancer cells apoptosis in a caspase-independent pathway, which was downregulation of SIRT1. Therefore, isoalantolactone may serve as a chemotherapeutic agent for the treatment of human breast cancer.
异土木香内酯具有多种生物活性。然而，它是否能治疗乳腺癌及其潜在机制在很大程度上尚不清楚。本研究旨在评估异土木香内酯对乳腺癌的抗癌作用，并探讨其分子机制。选用了两种人乳腺癌细胞系（MDA-MB-231 和 MCF-7）和一种正常乳腺细胞系（MCF-10A）。我们的数据表明，异土木香内酯呈剂量依赖性地降低乳腺癌细胞活力，但对 MCF-10A 细胞几乎没有毒性。异土木香内酯的抗癌作用与活性氧的过表达有关。异土木香内酯通过激活半胱天冬酶级联反应，裂解多聚（ADP-核糖）聚合酶，显著诱导乳腺癌细胞凋亡。Bax/Bcl-2 比值增加、线粒体膜电位去极化、细胞色素 c 从线粒体释放到细胞质以及细胞周期停滞在 G2/M 期与诱导凋亡有关。此外，异土木香内酯增加了 p38 MAPK 和 JNK 的蛋白表达。用 SB203580（p38 MAPK 抑制剂）或 SP600125（JNK 抑制剂）共同处理可阻断异土木香内酯的凋亡诱导。此外，异土木香内酯通过下调 SIRT1 诱导乳腺癌细胞发生 caspase 非依赖性凋亡。因此，异土木香内酯可能可作为治疗人类乳腺癌的化疗药物。
