Grifolin induces autophagic cell death by inhibiting the Akt/mTOR/S6K pathway in human ovarian cancer cells.
Grifolin, a secondary metabolic product isolated from the mushroom Albatrellus confluence, has been reported to possess antitumor activities in various tumors. To date, no report exists on the role of autophagy in grifolin-treated human ovarian cancer cells. In the present study, we investigated the effect and the mechanism of autophagy in ovarian cancer. Ovarian cancer cell lines A2780 and SKOV3 were treated with grifolin. Cell proliferation was assessed by MTT assay and the autophagic effect was determined using flow cytometry, electron microscopy, immunofluorescence staining and GFP-LC3 puncta formation assay. The expression of autophagy markers and the main autophagy-associated Akt/mTOR/S6K pathway proteins were measured by western blot analysis. MTT assay indicated that grifolin inhibits the proliferation of human ovarian cancer cell lines A2780 and SKOV3. Flow cytometry, electron microscopy, immunofluorescence and GFP-LC3 puncta formation assay proved that grifolin induces autophagic cell death in human ovarian cancer. The results of the western blot analysis suggested that grifolin treatment leads to upregulation of autophagy markers LC3B, Atg7, Beclin-1 along with downregulation of P62. In addition, the proteins of the pathways p-Akt, p-mTOR, p-p70S6K and p-4E-BP1 were downregulated while the total of these proteins remained unaffected. The present study indicated that grifolin could induce autophagic cell death in human ovarian cancer by inhibiting the Akt/mTOR/S6K pathway.
Department of Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China.
Xiaoxia
X
Che
Department of Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China.
Hong
H
Yan
Department of Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China.
Hengzi
H
Sun
Department of Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China.
Samina
S
Dongol
Department of Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China.
Yilin
Y
Wang
Shandong University of Traditional Chinese Medicine, Jinan, Shandong, P.R. China.
Qingtao
Q
Lv
Department of Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China.
Jie
J
Jiang
D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology
D051017:Apoptosis Regulatory Proteins; D013729:Terpenes; C058858:grifolin; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases