Effect of glutathione depletion on caspase-3 independent apoptosis pathwayinduced by curcumin in Jurkat cells

Curcumin, a yellow pigment from Curcuma longa, exhibits anti-inflammatory, antitumor, and antioxidative properties. Although its precise mode of actio n has not been elucidated so far, numerous studies have shown that curcumin may induce apoptosis in normal and cancer cells. Previously, we showed tha t in Jurkat cells curcumin induced nontypical apoptosis-like pathway, which was independent of mitochondria and caspase-3. Now we show that the inhibi tion of caspase-3 by curcumin, which is accompanied by attenuation of inter nucleosomal DNA fragmentation, may be due to elevation of glutathione, whic h increased in curcumin-treated cells to 130% of control. We have demonstra ted that glutathione depletion does not itself induce apoptosis in Jurkat c ells, though, it can release cytochrome c from mitochondria and caspase-3 f rom inhibition by curcumin, as shown by Western blot. The level of Bcl-2 pr otein was not affected by glutathione depletion even upon curcumin treatmen t. Altogether, our results show that in Jurkat cells curcumin prevents glut athione decrease, thus protecting cells against caspase-3 activation and ol igonucleosomal DNA fragmentation. On the other hand, it induces nonclassica l apoptosis via a Still-Unrecognized mechanism, which leads to chromatin de gradation and high-molecular-weight DNA fragmentation. (C) 2001 Elsevier Sc ience Inc.