title: Induction of apoptotic death by curcumin in human tongue squamous cell carcinoma SCC-4 cells is mediated through endoplasmic reticulum stress and mitochondria-dependent pathways.
abstract: Curcumin from the rhizome of the Curcuma longa plant has been noted for its chemo-preventative and chemo-therapy activities, and it inhibits the growth of many types of human cancer cell lines. In this study, the mechanisms of cell death involved in curcumin-induced growth inhibition, including cell cycle arrest and induction of apoptosis in human tongue cancer SCC-4 cells, were investigated. Herein, we observed that curcumin inhibited cell growth of SCC-4 cells and induced cell death in a dose-dependent manner. Treatment of SCC-4 cells with curcumin caused a moderate and promoted the G(2) /M phase arrest, which was accompanied with decreases in cyclin B/CDK1 and CDC25C protein levels. Moreover, curcumin significantly induced apoptosis of SCC-4 cells with a decrease of the Bcl-2 level, reduction of mitochondrial membrane potential (ΔΨ(m) ), and promoted the active forms of caspase-3. Curcumin also promoted the releases of AIF and Endo G from the mitochondria in SCC-4 cells by using confocal laser microscope. Therefore, we suggest that curcumin induced apoptosis through a mitochondria-dependent pathway in SCC-4 cells. In addition, we also found that curcumin-induced apoptosis of SCC-4 cells was partly through endoplasmic reticulum stress. In conclusion, curcumin increased G(2) /M phase arrest and induced apoptosis through ER stress and mitochondria-dependent pathways in SCC-4 cells.
authors: Department of Nutrition, China Medical University, Taichung, Taiwan.
authors: Siu-Wan
authors: SW
authors: Ip
authors: Shan-Ying
authors: SY
authors: Wu
authors: Chien-Chih
authors: CC
authors: Yu
authors: Chao-Lin
authors: CL
authors: Kuo
authors: Chun-Shu
authors: CS
authors: Yu
authors: Jai-Sing
authors: JS
authors: Yang
authors: Zen-Pin
authors: ZP
authors: Lin
authors: Shang-Ming
authors: SM
authors: Chiou
authors: Hsiung-Kwang
authors: HK
authors: Chung
authors: Heng-Chien
authors: HC
authors: Ho
authors: Jing-Gung
authors: JG
authors: Chung
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D030024:Curcuma / Q000737:chemistry; D003474:Curcumin / Q000494:pharmacology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D014062:Tongue Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D010936:Plant Extracts; D053148:Caspase 3; D003474:Curcumin