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Resveratrol induces growth inhibition and apoptosis in metastatic breast cancer cells via de novo ceramide signaling
Author(s) -
Scarlatti Francesca,
Sala Giusy,
Somenzi Giulia,
Signorelli Paola,
Sacchi Nicoletta,
Ghidoni Riccardo
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0292fje
Subject(s) - ceramide , resveratrol , sphingomyelin , lipid signaling , sphingolipid , apoptosis , chemistry , sphingomyelin phosphodiesterase , signal transduction , cell growth , microbiology and biotechnology , cancer research , biology , biochemistry , enzyme , membrane
Resveratrol (3,4‘,5‐ trans ‐trihydroxystilbene), a phytoalexin present in grapes and red wine, is emerging as a natural compound with potential anticancer properties. Here we show that resveratrol can induce growth inhibition and apoptosis in MDA‐MB‐231, a highly invasive and metastatic breast cancer cell line, in concomitance with a dramatic endogenous increase of growth inhibitory/proapoptotic ceramide. We found that accumulation of ceramide derives from both de novo ceramide synthesis and sphingomyelin hydrolysis. More specifically we demonstrated that ceramide accumulation induced by resveratrol can be traced to the activation of serine palmitoyltransferase (SPT), the key enzyme of de novo ceramide biosynthetic pathway, and neutral sphingomyelinase (nSMase), a main enzyme involved in the sphingomyelin/ceramide pathway. However, by using specific inhibitors of SPT, myriocin and L‐ cycloserine, and nSMase, gluthatione and manumycin, we found that only the SPT inhibitors could counteract the biological effects induced by resveratrol. Thus, resveratrol seems to exert its growth inhibitory/apoptotic effect on the metastatic breast cancer cell line MDA‐MB‐231 by activating the de novo ceramide synthesis pathway.