Involvement of PKC signal pathways in oridonin-induced autophagy in HeLa cells: a protective mechanism against apoptosis.
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.
Zhang
Yahong
Y
China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
Wu
Yingliang
Y
Tashiro
Shin-Ichi
S
Onodera
Satoshi
S
Ikejima
Takashi
T
D017209:Apoptosis; D001343:Autophagy; D019610:Cytoprotection; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction
D045786:Diterpenes, Kaurane; C011959:oridonin; D019908:Proto-Oncogene Proteins c-raf; D011493:Protein Kinase C; D048670:MAP Kinase Kinase 4