Diosgenin‑induced autophagy and apoptosis in a human prostate cancer cell line.
Diosgenin, a plant steroid compound from Dioscorea nipponica, is an anti-inflammatory, antidiabetic, antitumor, vasodilatory compound, which also reduces blood lipid content and protects against ischemia‑induced neuronal damage. However, a limited number of studies have been performed on the antitumor effect of diosgenin on prostate cancer, the underlying mechanism of which remains to be fully elucidated. In the present study, the effect and underlying mechanism of diosgenin on DU145 human prostate cancer cells was investigated. DU145 cells were cultured in vitro with diosgenin, following which cell proliferation was detected by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and apoptosis was detected by flow cytometry. In addition, DU145 cells were observed under a transmission electron microscope to confirm autophagy. monodansylcadaverine staining and western blotting indicated the levels of autophagy in DU145 cells. To determine the mechanism underlying the effect of diosgenin on DU145 cells, western blotting was performed to evaluate the involvement of the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. To investigate the association between apoptosis and autophagy, DU145 cells were cultured with diosgenin and 3‑methyladenine. Hoechst 33342/propidium iodide double staining was performed to detect apoptosis, and reverse transcription‑quantitative polymerase chain reaction was used to analyze mRNA expression levels of Beclin 1 and B‑cell lymphoma 2. Diosgenin inhibits the proliferation of DU145 cells by activating apoptosis and autophagy, and the mechanism underlying this activation may be associated with the inhibition of the PI3K/Akt/mTOR signaling pathway. In addition, the inhibition of autophagy mediated by diosgenin increases apoptosis and, thus, increases the therapeutic effect. The combination of diosgenin with an autophagy inhibitor may be an effective strategy to increase the antitumor effect of diosgenin.
Department of Research Office, Jiangsu Jiankang Vocational College, Nanjing, Jiangsu 211800, P.R. China.
Chao
C
Nie
Department of Research Office, Jiangsu Jiankang Vocational College, Nanjing, Jiangsu 211800, P.R. China.
Jie
J
Zhou
Nanjing KeyGen Biotech Co., Ltd., Nanjing, Jiangsu 211100, P.R. China.
Xiaokang
X
Qin
Department of Research Office, Jiangsu Jiankang Vocational College, Nanjing, Jiangsu 211800, P.R. China.
Xianming
X
Shi
Department of Research Office, Jiangsu Jiankang Vocational College, Nanjing, Jiangsu 211800, P.R. China.
Qingqi
Q
Zeng
Department of Research Office, Jiangsu Jiankang Vocational College, Nanjing, Jiangsu 211800, P.R. China.
Jia
J
Liu
Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
Shihai
S
Yan
Department of Research Office, Jiangsu Jiankang Vocational College, Nanjing, Jiangsu 211800, P.R. China.
Lei
L
Zhang
D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004144:Diosgenin / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051058:Oncogene Protein v-akt / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000235:genetics
D004144:Diosgenin; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human