TY - JOUR AB - Curcumin has been shown to exert potential antitumor activity in vitro and in vivo involved in multiple signaling pathways. However, the application of curcumin is still limited because of its poor hydrophilicity and low bio-availability. In the present study, we investigated the therapeutic effects of a novel and water soluble bis(hydroxymethyl) alkanoate curcuminoid derivative, MTH-3, on human breast adenocarcinoma MDA-MB-231 cells. This study investigated the effect of MTH-3 on cell viability, cell cycle and induction of autophagy and apoptosis in MDA-MB-231 cells. After 24-h treatment with MTH-3, a concentration-dependent decrease in MDA-MB-231 cell viability was observed, and the IC50 value was 5.37±1.22 µM. MTH-3 significantly triggered G2/M phase arrest and apoptosis in MDA-MB-231 cells. Within a 24-h treatment, MTH-3 decreased the CDK1 activity by decreasing CDK1 and cyclin B1 protein levels. MTH-3-induced apoptosis was further confirmed by morphological assessment and annexin V/PI staining assay. Induction of apoptosis caused by MTH-3 was accompanied by an apparent increase of DR3, DR5 and FADD and, as well as a marked decrease of Bcl-2 and Bcl-xL protein expression. MTH-3 also decreased the protein levels of Ero1, PDI, PERK and calnexin, as well as increased the expression of IRE1α, CHOP and Bip that consequently led to ER stress and MDA-MB-231 cell apoptosis. In addition, MTH-3-treated cells were involved in the autophagic process and cleavage of LC3B was observed. MTH-3 enhanced the protein levels of LC3B, Atg5, Atg7, Atg12, p62 and Beclin-1 in MDA-MB-231 cells. Finally, DNA microarray was carried out to investigate the level changes of gene expression modulated by MTH-3 in MDA-MB-231 cells. Taken together, our results suggest that MTH-3 might be a novel therapeutic agent for the treatment of triple-negative breast cancer in the near future. AD - Chinese Medicinal Research and Development Center, China Medical University Hospital, Taichung 404, R.O.C. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, R.O.C. Department of Pharmacy, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan, R.O.C. Human Genetic Center, China Medical University Hospital, Taichung 404, R.O.C. School of Pharmacy, China Medical University, Taichung 404, R.O.C. Division of Reconstructive and Plastic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 112, Taiwan, R.O.C. AU - Chang,Ling-Chu AU - Hsieh,Min-Tsang AU - Yang,Jai-Sing AU - Lu,Chi-Cheng AU - Tsai,Fuu-Jen AU - Tsao,Je-Wei AU - Chiu,Yu-Jen AU - Kuo,Sheng-Chu AU - Lee,Kuo-Hsiung DA - 2018/01/01 DO - 10.3892/ijo.2017.4204 EP - 76 IS - 1 JO - Int J Oncol KW - bis(hydroxymethyl) alkanoate curcuminoid derivative MTH-3 apoptosis autophagy breast cancer MDA-MB-231 cells PY - 2018 SN - 1019-6439 1791-2423 SP - 67 ST - Effect of bis(hydroxymethyl) alkanoate curcuminoid derivative MTH-3 on cell cycle arrest, apoptotic and autophagic pathway in triple-negative breast adenocarcinoma MDA-MB-231 cells: An in vitro study T2 - International Journal of Oncology TI - Effect of bis(hydroxymethyl) alkanoate curcuminoid derivative MTH-3 on cell cycle arrest, apoptotic and autophagic pathway in triple-negative breast adenocarcinoma MDA-MB-231 cells: An in vitro study UR - https://doi.org/10.3892/ijo.2017.4204 VL - 52 ER -