RACK-1 overexpression protects against goniothalamin-induced cell death.
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.
Inayat-Hussain
S H
SH
Toxicology and Biocompatibility Laboratory, Faculty of Allied Health Sciences, Universiti Kebangsaan Malaysia. salmaan@medic.ukm.my
Wong
L T
LT
Chan
K M
KM
Rajab
N F
NF
Din
L B
LB
Harun
R
R
Kizilors
A
A
Saxena
N
N
Mourtada-Maarabouni
M
M
Farzaneh
F
F
Williams
G T
GT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D003114:Colony-Forming Units Assay; D004396:Coloring Agents; D020552:Comet Assay; D003470:Culture Media; D004249:DNA Damage; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D009479:Neuropeptides / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011753:Pyrones / Q000633:toxicity*; D000075370:Receptors for Activated C Kinase; D013778:Tetrazolium Salts; D013844:Thiazoles
D004396:Coloring Agents; D003470:Culture Media; D009479:Neuropeptides; D011753:Pyrones; C090294:RACK1 protein, mouse; D000075370:Receptors for Activated C Kinase; D013778:Tetrazolium Salts; D013844:Thiazoles; C103280:goniothalamin; C022616:thiazolyl blue
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