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


METHODS
The 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.


RESULTS
We 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.


CONCLUSIONS
Our 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.
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi, Seoul, 130-701, Korea.
Hyeong Sim
HS
Choi
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi, Seoul, 130-701, Korea.
Min Kyoung
MK
Kim
Jeju International Marine Science Center for Research and Education, Korea Institute of Ocean Science & Technology (KIOST), Jeju, 695-975, Korea.|Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 1 Hoegi, Seoul, 130-701, Korea.
Youn Kyung
YK
Choi
Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 1 Hoegi, Seoul, 130-701, Korea.
Yong Cheol
YC
Shin
Department of Biotechnology, Korea National University of Transportation, 61 Daehakro, Jeungpyeong-gun, Chungbuk, 368-701, Korea. chosg@ut.ac.kr.
Sung-Gook
SG
Cho
Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 1 Hoegi, Seoul, 130-701, Korea. epiko@khu.ac.kr.
Seong-Gyu
SG
Ko
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D047188:Chalcones / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000494:pharmacology*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D029045:Rhus / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D047188:Chalcones; D010936:Plant Extracts; C040918:butein; D051057:Proto-Oncogene Proteins c-akt; D017239:Paclitaxel
AKT; Apoptosis; Butein; Paclitaxel-resistant ovarian cancer; Rhus verniciflua Stokes