Bee venom induces apoptosis through intracellular Ca 2+-modulated intrinsic death pathway in human bladder cancer cells

Siu Wan Ip, Yung Lin Chu, Chun Shu Yu, Po Yuan Chen, Heng Chien Ho, Jai Sing Yang, Hui Ying Huang, Fu Shin Chueh, Tung-Iuan Lai, Jing Gung Chung

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)61-70
Number of pages10
JournalInternational Journal of Urology
Volume19
Issue number1
DOIs
Publication statusPublished - Jan 2012

Keywords

  • Apoptosis
  • Bee venom
  • Endoplasmic reticulum stress
  • Human bladder cancer TSGH-8301 cells
  • Intracellular Ca release

ASJC Scopus subject areas

  • Urology

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    Ip, S. W., Chu, Y. L., Yu, C. S., Chen, P. Y., Ho, H. C., Yang, J. S., Huang, H. Y., Chueh, F. S., Lai, T-I., & Chung, J. G. (2012). Bee venom induces apoptosis through intracellular Ca 2+-modulated intrinsic death pathway in human bladder cancer cells. International Journal of Urology, 19(1), 61-70. https://doi.org/10.1111/j.1442-2042.2011.02876.x