Involvement of PKC signal pathways in oridonin-induced autophagy in HeLa cells: a protective mechanism against apoptosis

Yahong Zhang, Yingliang Wu, Shin-Ichi Tashiro, Satoshi Onodera, Takashi Ikejima
Biochemical and Biophysical Research Communications 2009 January 9, 378 (2): 273-8
Our previous studies showed that oridonin could induce both apoptosis and autophagy in HeLa cells, and this autophagy might be a protective mechanism against apoptosis. In this study, the roles of PKC signal pathways in oridonin-induced HeLa cell autophagy and apoptosis were further investigated. We found that inhibition of PKC significantly reduced oridonin-induced autophagy whereas markedly increased apoptosis, while pretreatment with PKC activator caused opposite results. Subsequently, the oridonin-induced autophagy was also suppressed by Raf-1 or JNK inhibition accompanied by the increase of apoptosis, but it was not affected by ERK or p38 inhibition. In addition, oridonin-induced protein levels of Raf-1, JNK and p-JNK were sharply downregulated by PKC inhibitor, and they were enhanced by PKC activator. Taken together, these results demonstrate that PKC enhances oridonin-induced autophagy against apoptosis through regulating its downstream factors Raf-1 and JNK in HeLa cells.

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