title: Curcumin induces the apoptosis of non-small cell lung cancer cells through a calcium signaling pathway.
abstract: Curcumin is known for its anti-proliferative effects in lung cancer cells. Studies have demonstrated that an increase in the levels of intracellular free calcium ([Ca2+]i) is involved in curcumin-induced apoptosis. In this study, we aimed to investigate the involvement of calcium overload in the anti-proliferative effects of curcumin on lung cancer cells and the possible mechanisms involved. A549 and H1299 lung cancer cells were incubated with serial diluted curcumin. MTT assay was used to assess the cytotoxic effects of curcumin on the lung cancer cells; the inositol 1,4,5-trisphosphate receptor (IP3R, a key regulator of [Ca2+]i signaling) was blocked by its specific inhibitor, xestospongin C (XSC). Hoechst 33342, Fura-2/AM and rhodamine 123 fluorescence staining was employed to detect the apoptosis, the [Ca2+]i level and mitochondrial potential in the lung cancer cells. The expression levels of B-cell lymphoma-2 (Bcl-2), cleaved caspase-3 and cleaved caspase-9, and the phosphorylation level of IP3R were evaluated by western blot analysis. Our results revealed that curcumin inhibited cell growth, increased the [Ca2+]i level and increased the apoptosis of the lung cancer cells in a concentration-dependent manner. However, XSC attenuated the increase in the [Ca2+]i level and apoptosis, and also reversed the curcumin-induced loss of mitochondrial potential potential. Treatment with curcumin downregulated the expression of Bcl-2, and elevated the phosphorylation level of IP3R in a concentration-dependent manner. However, this effect was not reversed by treatment with XSC. In conclusion, the cytotoxic effects of curcumin on lung cancer cells were induced by calcium overload, which involves Bcl-2 mediated IP3R phosphorylation.
authors.affiliation: Department of Thoracic Surgery, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Thoracic Surgery, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Da
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Ye
authors.affiliation: Department of Thoracic Surgery, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Fangming
authors.initials: F
authors.lastname: Zhong
authors.affiliation: Department of Thoracic Surgery, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020013:Calcium Signaling / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D003474:Curcumin