title: Activation of AMP-Activated Protein Kinase α and Extracelluar Signal-Regulated Kinase Mediates CB-PIC-Induced Apoptosis in Hypoxic SW620 Colorectal Cancer Cells.
abstract: Here, antitumor mechanism of cinnamaldehyde derivative CB-PIC was elucidated in human SW620 colon cancer cells. CB-PIC significantly exerted cytotoxicity, increased sub-G1 accumulation, and cleaved PARP with apoptotic features, while it enhanced the phosphorylation of AMPK alpha and ACC as well as activated the ERK in hypoxic SW620 cells. Furthermore, CB-PIC suppressed the expression of HIF1 alpha, Akt, and mTOR and activated the AMPK phosphorylation in hypoxic SW620 cells. Conversely, silencing of AMPK α blocked PARP cleavage and ERK activation induced by CB-PIC, while ERK inhibitor PD 98059 attenuated the phosphorylation of AMPK α in hypoxic SW620 cells, implying cross-talk between ERK and AMPK α . Furthermore, cotreatment of CB-PIC and metformin enhanced the inhibition of HIF1 α and Akt/mTOR and the activation of AMPK α and pACC in hypoxic SW620 cells. In addition, CB-PIC suppressed the growth of SW620 cells inoculated in BALB/c athymic nude mice, and immunohistochemistry revealed that CB-PIC treatment attenuated the expression of Ki-67, CD34, and CAIX and increased the expression of pAMPK α in CB-PIC-treated group. Interestingly, CP-PIC showed better antitumor activity in SW620 colon cancer cells under hypoxia than under normoxia, since it may be applied to chemoresistance. Overall, our findings suggest that activation of AMPK α and ERK mediates CB-PIC-induced apoptosis in hypoxic SW620 colon cancer cells.
authors.affiliation: College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Sung-Yun
authors.initials: SY
authors.lastname: Cho
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Hyo-Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Deok-Beom
authors.initials: DB
authors.lastname: Jung
authors.forename: Hyunseok
authors.initials: H
authors.lastname: Kim
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Sohn
authors.forename: Bonglee
authors.initials: B
authors.lastname: Kim
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jung
authors.forename: Byoung-Mog
authors.initials: BM
authors.lastname: Kwon
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim