Protodioscin inhibits bladder cancer cell migration and growth, and promotes apoptosis through activating JNK and p38 signaling pathways.

Autor: Chen YR; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan., Wang SC; Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan., Huang SP; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; 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; Ph.D. Program in Environmental and Occupational 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., 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 Tumor Medical Science, China Medical University, Taichung 404333, Taiwan; Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung 404333, Taiwan., Chuu CP; Institute of Cellular and System Medicine, National Health Research Institutes, 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., Lee CH; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan., Ke CC; Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung 80708, Taiwan., Wu HE; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan., Chang HH; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan., Yeh HC; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Department of Urology, Kaohsiung Medical University Hospital, 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 Municipal Ta-Tung Hospital, Kaohsiung 80145, Taiwan. Electronic address: patrick1201.tw@yahoo.com.tw., Li CY; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan. Electronic address: chiayangli@kmu.edu.tw.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2022 Dec; Vol. 156, pp. 113929. Date of Electronic Publication: 2022 Oct 29.
DOI: 10.1016/j.biopha.2022.113929
Abstrakt: Bladder cancer is one of the most common malignancies of the male genitourinary urinary system. Protodioscin is a steroidal saponin with anti-cancer effects on several types of cancers; however, the anti-cancer activities of protodioscin on bladder cancer have not yet been investigated. Therefore, we aimed to examine the anti-cancer effects of protodioscin on bladder cancer. Two types of bladder cancer cell lines, non-muscle-invasive 5637 cells and muscle-invasive T24 cells, were used to evaluate the effects of protodioscin on cell growth, migration, invasion and epithelial-mesenchymal transition(EMT) marker expressions. Transcriptome analysis was performed by RNA-seq and validated using real-time PCR and western blot; additionally, an in vivo xenograft animal model was established and the anti-tumor effects of protodioscin were tested. Our results demonstrated that protodioscin inhibited cell proliferation, migration, motility and invasion on 5637 and T24 cells. Additionally, protodioscin also induced cell apoptosis and arrested the progression of cell cycle at G2 phase in bladder cancer cells. Moreover, protodioscin inhibited EMT through increased protein expression of E-cadherin and decreased protein expression of N-cadherin and vimentin. RNA-seq analysis indicated that protodioscin regulated mitogen-activated protein kinase(MAPK) and phosphoinositide 3-kinases(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR) signaling pathways as further verified by Western blot. Furthermore, protodioscin significantly inhibited tumor growth in vivo. Our results indicated that protodioscin inhibits cell growth, migration and invasion and induces apoptosis and G2 phase cell cycle arrest by activated p38 and JNK signaling pathways in bladder cancer cells, suggesting that protodioscin could be an effective agent for bladder cancer treatment.
Competing Interests: Declaration of Competing Interest The authors declare no competing interests.
(Copyright © 2022. Published by Elsevier Masson SAS.)
Databáze: MEDLINE
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