ERK-modulated intrinsic signaling and G(2)/M phase arrest contribute to the induction of apoptotic death by allyl isothiocyanate in MDA-MB-468 human breast adenocarcinoma cells

作者：Tsai Shih Chang; Huang Wen Wen; Huang Wei Chien; Lu Chi Cheng; Chiang Jo Hua; Peng Shu Fen; Chung Jing Gung; Lin Yu Hsin; Hsu Yuan Man; Amagaya Sakae; Yang Jai Sing^*

来源：International Journal of Oncology, 2012, 41(6): 2065-2072.

DOI：10.3892/ijo.2012.1640

• AITC
• apoptosis
• G(2)/M phase arrest
• mitochondria
• ERK
• human breast cancer MDA-MB-468 cells

Allyl isothiocyanate (AITC), a member of the isothiocyanate (ITC) family found in a constituent of cruciferous vegetables, possesses anticancer activity and induces apoptosis in various types of human cancer cell lines. However, no available information showed antitumor effects in human breast adenocarcinoma cells. The current study was focused on exploring the mechanisms underlying AITC-induced apoptosis in MDA-MB-468 human breast cancer cells in vitro. We found that AITC reduced the cell number and viability using trypan blue staining with the Countess Automated Cell Counter and the MTT assay, respectively. AITC also was found to induce apoptotic cell morphological changes by a contrast-phase microscope and cell cycle arrest at G(2)/M phase by flow cytometric assay in MDA-MB-468 cells. Intrinsic apoptosis-associated factors such as caspase-9 and caspase-3 activities were performed, and reactive oxygen species (ROS) production, loss of mitochondrial membrane potential (Delta Psi m) occurred in AITC-treated MDA-MB-468 cells. A ITC also stimulated mitochondria-related signaling, including p-Bc1-2 (Ser-70), cytochrome c and Apaf-1 in MDA-MB-468 cells. We found that the p-ERK signal was upregulated in AITC-treated cells. Importantly, NAC (a ROS scavenger) and U0126 (an ERK inhibitor) abolished AITC-reduced viability in MDA-MB-468 cells. A ITC downregulated CDK1 activity and altered the expression of G(2)/M phase-modulated associated protein levels by western blotting in MDA-MB-468 cells. In summary, our findings demonstrated that AITC-promoted G(2)/M phase and AITC-triggered apoptosis correlate with the activation of phosphorylation of ERK in MDA-MB-468 cells. Arrc is a potential agent for applcation in the treatment of human breast cancer.

• 出版日期2012-12
• 单位中国医科大学