title: Autophagy induced by farnesyltransferase inhibitors in cancer cells.
abstract: The mechanisms of action of farnesyltransferase inhibitors (FTIs) involve Rheb and the phosphatidylinositide 3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway. mTOR in particular plays a key role in the regulation of autophagy. Collectively, the literature suggests that FTIs very likely induce autophagy, but thus far there have been no reports that FTIs affect this process relevant to cancer cell biology. We hypothesized that FTIs can induce autophagy. In this study, we found that the FTIs manumycin A, FTI-276, and lonafarnib induced autophagy in two human cancer cell lines. We also found that neither inhibition of apoptosis with a pan-caspase inhibitor nor inhibition of autophagy increased the number of clones of lonafarnib-treated U2OS osteosarcoma cells that formed in soft agar. Although whether autophagy is a cell death or cell survival mechanism after FTI treatment remains unresolved, our data show that cancer cells apparently can shift between apoptosis and autophagy once they are committed to die after FTI treatment.
authors.affiliation: Department of Pathophysiology, Sun Yat-Sen University Medical School, Guangzhou, Guangdong, PR China. jingx_pan@yahoo.com.cn
authors.forename: Jingxuan
authors.initials: J
authors.lastname: Pan
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Chun-Hui
authors.initials: CH
authors.lastname: Su
authors.forename: Ruiying
authors.initials: R
authors.lastname: Zhao
authors.forename: Zhi-Xiang
authors.initials: ZX
authors.lastname: Xu
authors.forename: Lily
authors.initials: L
authors.lastname: Sun
authors.forename: Mong-Hong
authors.initials: MH
authors.lastname: Lee
authors.forename: Sai-Ching Jim
authors.initials: SC
authors.lastname: Yeung