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Wogonin induces cross‐regulation between autophagy and apoptosis via a variety of Akt pathway in human nasopharyngeal carcinoma cells
Author(s) -
Chow ShuEr,
Chen YuWen,
Liang ChiAng,
Huang YaoKuan,
Wang JongShyan
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24224
Subject(s) - wogonin , autophagy , protein kinase b , pi3k/akt/mtor pathway , apoptosis , chemistry , microbiology and biotechnology , mapk/erk pathway , lamp1 , atg5 , cancer research , signal transduction , biology , scutellaria baicalensis , biochemistry , medicine , traditional chinese medicine , alternative medicine , pathology
Autophagy as well as apoptosis is an emerging target for cancer therapy. Wogonin, a flavonoid compound derived from the traditional Chinese medicine of Huang‐Qin, has anticancer activity in many cancer cells including human nasopharyngeal carcinoma (NPC). However, the involvement of autophagy in the wogonin‐induced apoptosis of NPC cells was still uninvestigated. In this study, we found wogonin‐induced autophagy had interference on the process of apoptosis. Wogonin‐induced autophagy formation evidenced by LC3 I/II cleavage, acridine orange (AO)‐stained vacuoles and the autophagosome/autolysosome images of TEM analysis. Activation of autophagy with rapamycin resulted in increased wogonin‐mediated autophagy via inhibition of mTOR/P70S6K pathway. The functional relevance of autophagy in the antitumor activity was investigated by annexin V‐positive stained cells and PARP cleavage. Induction of autophagy by rapamycin ameliorated the wogonin‐mediated apoptosis, whereas inhibition of autophagy by 3‐methyladenine (3‐MA) or bafilomycin A1 increased the apoptotic effect. Interestingly, this study also found, in addition the mTOR/P70S6K pathway, wogonin also inhibited Raf/ERK pathway, a variety of Akt pathways. Inactivation of PI 3 K/Akt by their inhibitors significantly induced apoptosis and markedly sensitized the NPC cells to wogonin‐induced apoptosis. This anticancer effect of Akt was further confirmed by SH6, a specific inhibitor of Akt. Importantly, inactivation of its downstream molecule ERK by PD98059, a MEK inhibitor, also induced apoptosis. This study indicated wogonin‐induced both autophagy and apoptosis through a variety of Akt pathways and suggested modulation of autophagy might provide profoundly the potential therapeutic effect. J. Cell. Biochem. 113: 3476–3485, 2012. © 2012 Wiley Periodicals, Inc.