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Apoptotic Effects and Cell Cycle Arrest Effects of Extracts from Cnidium monnieri (L.) Cusson through Regulating Akt/mTOR/GSK-3β Signaling Pathways in HCT116 Colon Cancer Cells

HCT116 대장암세포에서 AKT/mTOR/GSK-3β 신호경로 조절을 통한 벌 사상자 추출물(CME)의 apoptosis 및 cell cycle arrest 효과

Lim, Eun Gyeong;Kim, Guen Tae;Kim, Bo Min;Kim, Eun Ji;Ha, Sung Ho;Kim, Sang-Yong;Kim, Young Min
임은경;김근태;김보민;김은지;하성호;김상용;김영민

  • Received : 2016.03.17
  • Accepted : 2016.05.25
  • Published : 2016.06.30

Abstract

The Cnidium monnieri (L.) Cusson is an annual plant distributed in China and Korea. The fruit of C. monnieri is used as a medicinal herb that is effective for the treatment of carbuncle and pain in female genitalia. However, the anti-cancer effects of CME have not yet been reported. In this study, we assessed the apoptotic effects and cell cycle arrest effects of ethanol extracts from C. monnieri on HCT116 colon cancer cells. The results of an MTT assay and LDH assay demonstrated a decrease in cell viability and the cytotoxic effects of CME. In addition, the number of apoptotic body and the apoptotic rate were increased in a dose-dependent manner through Hoechst 33342 staining and Annexin V-PI double staining. In addition, cell cycle arrest occurred at the G1 phase by CME. Protein kinase B (Akt) plays an important role in cancer cell survival, growth, and division. Akt down-regulates apoptosis-mediated proteins, such as mammalian target of rapamycin (mTOR), p53, and Glycogen Synthase kinase-3β (GSK-3β). CME could regulate the expression levels of p-Akt, p-mTOR, p-GSK-3β, Bcl-2 family members, caspase-3, and PARP. Furthermore, treatment with CME, LY294002 (PI3K/Akt inhibitor), BIO (GSK-3β inhibitor), and Rapamycin (mTOR inhibitor) showed that apoptotic effects occurred through the regulation of the AKT/mTOR/GSK-3β signaling pathway. Our results demonstrated CME could induce apoptosis and cell cycle arrest in HCT116 colon cancer cells.

Keywords

AKT/mTOR/GSK-3βpathway;apoptosis;cell cycle arrest;CME;HCT116

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