Methyl lucidone induces apoptosis and G2/M phase arrest via the PI3K/Akt/NF-κB pathway in ovarian cancer cells

Pharmaceutical Biology

Jae-Hwan Yoon¹  Jong-Woon Shin¹  Do-Young Yoon¹  Thu-Huyen Pham¹  Youn-Jin Choi²  Jae-Wook Oh³  Sei-Ryang Oh⁴  Hyung-Won Ryu⁴ 

[1] Department of Bioscience and Biotechnology, Research Institute of Bioactive-Metabolome Network, Konkuk University;Department of Obstetrics and Gynecology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea;Department of Stem Cell and Regenerative Biotechnology, Konkuk University;Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology;

关键词: lindera erythrocarpa makino;    cell death;    cell cycle arrest;    ovcar-8;    skov-3;   

DOI  :  10.1080/13880209.2019.1701044

来源: DOAJ

【 摘 要 】

Context Methyl lucidone (ML) from the dried fruit of Lindera erythrocarpa Makino (Lauraceae) exhibits cytotoxic effects in various cancer cell lines. However, its effects on ovarian cancer cells remain unknown. Objective This study evaluates the mechanism of ML-induced apoptosis, cell cycle distribution in ovarian cells. Materials and methods The cytotoxic effect of ML (2.5–80 µM) on OVCAR-8 and SKOV-3 cells was evaluated by MTS assay for 24 and 48 h. Apoptosis and cell cycle arrest were analysed by flow cytometry. PCR, western blot analyses were performed to examine the related signalling pathways. Results ML induced significant cellular morphological changes and apoptosis in ovarian cancer cells, leading to an antiproliferative effect (IC50 = 33.3–54.7 µM for OVCAR-8 and 48.8-60.7 µM for SKOV-3 cells). Treatment with ML induced cleavage of caspase-3/9 and PARP and release of cytochrome c from the mitochondria. Moreover, ML downregulated the expression of Bcl-2 and Bcl-xL and induced cell cycle arrest in the G2/M phase. Additionally, ML suppressed the expression of cyclin-A/B and promoted that of the cyclin-dependent kinase inhibitors p21 and p27. The expression of death receptors was not altered. Interestingly, ML also inhibited the activity of PI3K/Akt and NF-κB. Discussion and conclusions ML caused G2/M phase arrest and apoptosis in ovarian cancer cells by activating intrinsic apoptotic pathways and suppressing the PI3K/Akt survival pathway. ML may be a potential anticancer agent to suppress ovarian cancer proliferation; thus, to improve the survival rate of cancer patients.

【 授权许可】

Unknown