Kan Ping-Chuan, Chang Yu-Jia, Chien Chin-Sung, Su Chen-Ying, Fang Hsu-Wei
Graduate Institute of Biochemical and Biomedical Engineering, National Taipei University of Technology, Taipei, Taiwan, R.O.C.
Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan, R.O.C.
Anticancer Res. 2018 Nov;38(11):6253-6261. doi: 10.21873/anticanres.12981.
BACKGROUND/AIM: Dichloroacetate (DCA) and curcumin have been shown to be potent drug candidates in cancer therapy. Our study aimed to investigate the combined effects of DCA and essential oil-blended curcumin (ECUR) using the hepatoma Huh-7 cell model.
Muse™ Cell Cycle assay, Muse™ Annexin V & Dead Cell assay, Muse™ Oxidative Stress assay, and western blot analysis were applied to explore the underlying mechanisms.
DCA combined with ECUR dramatically augmented inhibition of cell survival and enhanced apoptotic induction. The enhanced apoptosis was accompanied by mitochondria-dependent apoptotic signaling activation and corroborated with significant cellular morphological alternations.
Apoptosis was the major event contributing to the synergistically boosted antiproliferative effect. Coupling DCA treatment with curcumin may rationally be expected to lower the DCA dose needed and relatively reduce accompanying toxicity and oxidative damage while enhancing anticancer potential. This novel 'add-on' approach is, thus, of enormous value to the current DCA therapy.
背景/目的:二氯乙酸(DCA)和姜黄素已被证明是癌症治疗中有潜力的候选药物。我们的研究旨在使用肝癌Huh-7细胞模型研究DCA与精油混合姜黄素(ECUR)的联合作用。
应用Muse™细胞周期分析、Muse™膜联蛋白V和死细胞分析、Muse™氧化应激分析以及蛋白质印迹分析来探究潜在机制。
DCA与ECUR联合显著增强了对细胞存活的抑制作用并增强了凋亡诱导。凋亡增强伴随着线粒体依赖性凋亡信号激活,并伴有明显的细胞形态学改变。
凋亡是导致协同增强的抗增殖作用的主要事件。将DCA治疗与姜黄素联合使用可能合理地预期会降低所需的DCA剂量,并相对减少伴随的毒性和氧化损伤,同时增强抗癌潜力。因此,这种新颖的“附加”方法对当前的DCA治疗具有巨大价值。