Anticancer Effects of Morusin in Prostate Cancer via Inhibition of Akt/mTOR Signaling Pathway.

Autor: Wu HE; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan., Su CC; Division of Urology, Department of Surgery, Chi-Mei Medical Center, Tainan 71004, Taiwan.; Department of Senior Citizen Service Management, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan., Wang SC; Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan., Liu PL; Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan., Cheng WC; Graduate Institute of Biomedical Sciences and Research Center for Cancer Biology, China Medical University, Taichung 404333, Taiwan.; Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung 404333, Taiwan., Yeh HC; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.; Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.; Department of Urology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.; Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80145, Taiwan., Chuu CP; Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Miaoli County 35053, Taiwan., Chen JK; Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli County 35053, Taiwan., Bao BY; Department of Pharmacy, China Medical University, Taichung 404333, Taiwan.; Department of Nursing, Asia University, Taichung 41354, Taiwan., Lee CH; Department of Urology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan., Ke CC; Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung 80708, Taiwan., Chen YR; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan., Yu YH; School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan., Huang SP; Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.; Department of Urology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.; Ph.D. Program in Environmental and Occupational Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan., Li CY; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.; Department of Medical Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.; Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan.
Jazyk: angličtina
Zdroj: The American journal of Chinese medicine [Am J Chin Med] 2023; Vol. 51 (4), pp. 1019-1039. Date of Electronic Publication: 2023 Apr 29.
DOI: 10.1142/S0192415X23500477
Abstrakt: Prostate cancer (PCa) is the second most prevalent cancer in men worldwide. The majority of PCa incidences eventually progress to castration-resistant PCa (CRPC), thereby establishing an urgent need for new effective therapeutic strategies. This study aims to examine the effects of morusin, a prenylated flavonoid isolated from Morus alba L., on PCa progression and identify the regulatory mechanism of morusin. Cell growth, cell migration and invasion, and the expression of EMT markers were examined. Cycle progression and cell apoptosis were examined using flow cytometry and a TUNEL assay, while transcriptome analysis was performed using RNA-seq with results being further validated using real-time PCR and western blot. A xenograft PCa model was used to examine tumor growth. Our experimental results indicated that morusin significantly attenuated the growth of PC-3 and 22Rv1 human PCa cells; moreover, morusin significantly suppressed TGF-[Formula: see text]-induced cell migration and invasion and inhibited EMT in PC-3 and 22Rv1 cells. Significantly, morusin treatment caused cell cycle arrest at the G2/M phase and induced cell apoptosis in PC-3 and 22Rv1 cells. Morusin also attenuated tumor growth in a xenograft murine model. The results of RNA-seq indicated that morusin regulated PCa cells through the Akt/mTOR signaling pathway, while our western blot results confirmed that morusin suppressed phosphorylation of AKT, mTOR, p70S6K, and downregulation of the expression of Raptor and Rictor in vitro and in vivo . These results suggest that morusin has antitumor activities on regulating PCa progression, including migration, invasion, and formation of metastasis, and might be a potential drug for CRPC treatment.
Databáze: MEDLINE