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Bee venom induces apoptosis through intracellular Ca 2+ ‐modulated intrinsic death pathway in human bladder cancer cells
Author(s) -
Ip SiuWan,
Chu YungLin,
Yu ChunShu,
Chen PoYuan,
Ho HengChien,
Yang JaiSing,
Huang HuiYing,
Chueh FuShin,
Lai TungYuan,
Chung JingGung
Publication year - 2012
Publication title -
international journal of urology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.172
H-Index - 67
eISSN - 1442-2042
pISSN - 0919-8172
DOI - 10.1111/j.1442-2042.2011.02876.x
Subject(s) - medicine , apoptosis , intracellular , programmed cell death , bladder cancer , cancer research , cancer cell , microbiology and biotechnology , cancer , biochemistry , biology
Objectives: To focus on bee venom‐induced apoptosis in human bladder cancer TSGH‐8301 cells and to investigate its signaling pathway to ascertain whether intracellular calcium iron (Ca 2+ ) is involved in this effect. Methods: Bee venom‐induced cytotoxic effects, productions of reactive oxygen species and Ca 2+ and the level of mitochondrial membrane potential (ΔΨm) were analyzed by flow cytometry. Apoptosis‐associated proteins were examined by Western blot analysis and confocal laser microscopy. Results: Bee venom‐induced cell morphological changes and decreased cell viability through the induction of apoptosis in TSGH‐8301 cell were found. Bee venom promoted the protein levels of Bax, caspase‐9, caspase‐3 and endonuclease G. The enhancements of endoplasmic reticulum stress‐related protein levels were shown in bee venom‐provoked apoptosis of TSGH‐8301 cells. Bee venom promoted the activities of caspase‐3, caspase‐8, and caspase‐9, increased Ca 2+ release and decreased the level of ΔΨm. Co‐localization of immunofluorescence analysis showed the releases of endonuclease G and apoptosis‐inducing factor trafficking to nuclei for bee venom‐mediated apoptosis. The images revealed evidence of nuclear condensation and formation of apoptotic bodies by 4′,6‐diamidino‐2‐phenylindole staining and DNA gel electrophoresis showed the DNA fragmentation in TSGH‐8301 cells. Conclusions: Bee venom treatment induces both caspase‐dependent and caspase‐independent apoptotic death through intracellular Ca 2+ ‐modulated intrinsic death pathway in TSGH‐8301 cells.