RACK-1 overexpression protects against goniothalamin-induced cell death

Inayat-Hussain, S.H.; Wong, L.T.; Chan, K.M.; Rajab, N.F.; Din, L.B.; Harun, R.; Kizilors, A.; Saxena, N.; Mourtada-Maarabouni, M.; Farzaneh, F.; Williams, G.T.

Abstract

Goniothalamin, a styryllactone, has been shown to induce cytotoxicity via apoptosis in several tumor cell lines. In this study, we have examined the potential role of several genes, which were stably transfected into T-cell lines and which regulate apoptosis in different ways, on goniothalamin-induced cell death. Overexpression of full-length receptor for activated protein C-kinase 1 (RACK-1) and pc3n3, which up-regulates endogenous RACK-1, in both Jurkat and W7.2 T cells resulted in inhibition of goniothalamin-induced cell death as assessed by MTT and clonogenic assays. However, overexpression of rFau (antisense sequence to Finkel–Biskis–Reilly murine sarcoma virus-associated ubiquitously expressed gene) in W7.2 cells did not confer resistance to goniothalamin-induced cell death. Etoposide, a clinically used cytotoxic agent, was equipotent in causing cytotoxicity in all the stable transfectants. Assessment of DNA damage by Comet assay revealed goniothalamin-induced DNA strand breaks as early as 1 h in vector control but this effect was inhibited in RACK-1 and pc3n3 stably transfected W7.2 cells. This data demonstrate that RACK-1 plays a crucial role in regulating cell death signalling pathways induced by goniothalamin.

Citation

Inayat-Hussain, S., Wong, L., Chan, K., Rajab, N., Din, L., Harun, R., …Williams, G. (2009). RACK-1 overexpression protects against goniothalamin-induced cell death. Toxicology Letters, 191(2-3), 118-122. https://doi.org/10.1016/j.toxlet.2009.08.012

• Journal Article Type: Article
• Acceptance Date: Aug 12, 2009
• Online Publication Date: Aug 19, 2009
• Publication Date: Dec 15, 2009
• Deposit Date: May 16, 2024
• Journal: Toxicology Letters
• Print ISSN: 0378-4274
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 191
• Issue: 2-3
• Pages: 118-122
• ISBN: 03784274
• DOI: https://doi.org/10.1016/j.toxlet.2009.08.012
• Public URL: https://keele-repository.worktribe.com/output/543743