Monascuspiloin enhances the radiation sensitivity of human prostate cancer cells by stimulating endoplasmic reticulum stress and inducing autophagy.
Prostate cancer is a very common cancer among males. Traditional treatments for prostate cancer have limited efficacy; therefore, new therapeutic strategies and/or new adjuvant drugs must be explored. Red yeast rice (RYR) is a traditional food spice made in Asia by fermenting white rice with Monascus purpureus Went yeast. Accumulating evidence indicates that RYR has antitumor activity. In this study, PC-3 cells (human prostate cancer cells) were used to investigate the anti-cancer effects of ionizing radiation (IR) combined with monascuspiloin (MP, a yellow pigment isolated from Monascus pilosus M93-fermented rice) and to determine the underlying mechanisms of these effects in vitro and in vivo. We found that IR combined with MP showed increased therapeutic efficacy when compared with either treatment alone in PC-3 cells. In addition, the combined treatment enhanced DNA damage and endoplasmic reticulum (ER) stress. The combined treatment induced primarily autophagy in PC-3 cells, and the cell death that was induced by the combined treatment was chiefly the result of inhibition of the Akt/mTOR signaling pathways. In an in vivo study, the combination treatment showed greater anti-tumor growth effects. These novel findings suggest that the combined treatment could be a potential therapeutic strategy for prostate cancer.
Department of Environmental and Occupational Health, National Cheng Kung University, Medical College, Tainan, Taiwan.
Hui-Wen
HW
Chiu
Wen-Hung
WH
Fang
Yen-Lin
YL
Chen
Ming-Der
MD
Wu
Gwo-Fang
GF
Yuan
Sheng-Yow
SY
Ho
Ying-Jan
YJ
Wang
D000818:Animals; D001343:Autophagy / Q000187:drug effects; D001688:Biological Products / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006575:Heterocyclic Compounds, 3-Ring / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*
D001688:Biological Products; D006575:Heterocyclic Compounds, 3-Ring; D011838:Radiation-Sensitizing Agents; C576322:monascuspiloin; C117343:red yeast rice; D051057:Proto-Oncogene Proteins c-akt