Structure-activity requirements for the antiproliferative effect of troglitazone derivatives mediated by depletion of intracellular calcium.
Depletion of calcium from the endoplasmic reticulum has shown to affect protein synthesis and cell proliferation. The anticancer effect of troglitazone was reported to be mediated by depletion of intracellular calcium stores resulting in inhibition of translation initiation. The unsaturated form of troglitazone displays similar anticancer properties in vitro. In this letter, we report our findings on the minimum structural requirements for both compounds to retain their calcium release and antiproliferative activities.
Fan
Yun-Hua
YH
Laboratory for Translational Research, Harvard Medical School, Cambridge, MA 02139, USA. yunhuafan@yahoo.com
Chen
Han
H
Natarajan
Amarnath
A
Guo
Yuhong
Y
Harbinski
Fred
F
Iyasere
Julia
J
Christ
William
W
Aktas
Huseyin
H
Halperin
Jose A
JA
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002839:Chromans / Q000138:chemical synthesis / Q000494:pharmacology*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000138:chemical synthesis / Q000494:pharmacology*; D000077288:Troglitazone
D000970:Antineoplastic Agents; D002839:Chromans; D015852:Eukaryotic Initiation Factor-2; D045162:Thiazolidinediones; D000077288:Troglitazone; D002118:Calcium