Rhus verniciflua Stokes (RVS) and butein induce apoptosis of paclitaxel-resistant SKOV-3/PAX ovarian cancer cells through inhibition of AKT phosphorylation

BMC Complementary and Alternative Medicine

Research Article

Sung-Gook Cho¹  Seong-Gyu Ko²  Yong Cheol Shin²  Min Kyoung Kim³  Hyeong Sim Choi³  Youn Kyung Choi⁴ 

[1] Department of Biotechnology, Korea National University of Transportation, 61 Daehakro, Jeungpyeong-gun, 368-701, Chungbuk, Korea;Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 1 Hoegi, 130-701, Seoul, Korea;Department of Science in Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi, 130-701, Seoul, Korea;Jeju International Marine Science Center for Research and Education, Korea Institute of Ocean Science & Technology (KIOST), 695-975, Jeju, Korea;Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 1 Hoegi, 130-701, Seoul, Korea;

关键词: Rhus verniciflua;    Butein;    AKT;    Paclitaxel-resistant ovarian cancer;    Apoptosis;   

DOI  :  10.1186/s12906-016-1103-3

 received in 2016-01-08, accepted in 2016-04-21,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundRhus verniciflua Stokes (RVS) belongs to the Anacardiaceae family and traditionally used for cancer treatment. RVS and butein, a major compound of RVS, were known to induce apoptosis via AKT inhibition in cancer cells. Thus, in this study, we investigated the effect of RVS and its derivative compounds (fisetin, quercetin, butein) on cell death in SKOV-3/PAX cells.MethodsThe 80 % ethanol extract of RVS and its derivative compounds (fisetin, quercetin, butein) were prepared. The cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Apoptotic cells were detected by staining with propidium iodide (PI) and Annexin V-fluorescein isothiocyanate/7-aminoactinomycin D (Annexin V-FITC/7-AAD). The expression level of intracellular signaling related-proteins in apoptosis and growth were measured by western blot assay.ResultsWe found that RVS and butein suppressed the growth of SKOV-3/PAX cells in a dose-dependent manner. We also found that RVS and butein produced the cleavage of caspase-9, -8, -3, and PARP. Similarly, sub-G1 phase and Annexin V-FITC positive cells were increased by RVS and butein. Moreover, RVS and butein significantly reduced AKT phosphorylation in SKOV-3/PAX cells. PI3K inhibitor LY294002 caused PARP cleavage supporting our finding.ConclusionOur data clearly indicate that RVS and butein induce apoptosis of SKOV-3/PAX cells through inhibition of AKT activation. RVS and butein could be useful compounds for the treatment for paclitaxel resistant-ovarian cancer.

【 授权许可】

CC BY   
© Choi et al. 2016