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- Title
Anticancer Effects of Morusin in Prostate Cancer via Inhibition of Akt/mTOR Signaling Pathway.
- Authors
Wu, Hsin-En; Su, Chia-Cheng; Wang, Shu-Chi; Liu, Po-Len; Cheng, Wei-Chung; Yeh, Hsin-Chih; Chuu, Chih-Pin; Chen, Jen-Kun; Bao, Bo-Ying; Lee, Cheng Hsueh; Ke, Chien-Chih; Chen, Yuan-Ru; Yu, Yun-Hsin; Huang, Shu-Pin; Li, Chia-Yang
- Abstract
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- β -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.
- Subjects
IN vitro studies; DISEASE progression; FLAVONOIDS; IN vivo studies; SEQUENCE analysis; XENOGRAFTS; ANIMAL experimentation; WESTERN immunoblotting; ANTINEOPLASTIC agents; MTOR inhibitors; APOPTOSIS; RNA; CELLULAR signal transduction; TREATMENT effectiveness; CASTRATION-resistant prostate cancer; EPITHELIAL-mesenchymal transition; PEARSON correlation (Statistics); CELL migration inhibition; CHALONES; GENE expression profiling; PLANT extracts; DATA analysis software; MOLECULAR structure; PROSTATE tumors; MICE; PHOSPHORYLATION; PHARMACODYNAMICS
- Publication
American Journal of Chinese Medicine, 2023, Vol 51, Issue 4, p1019
- ISSN
0192-415X
- Publication type
Article
- DOI
10.1142/S0192415X23500477