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

Hsin En Wu, Chia Cheng Su, Shu Chi Wang, Po Len Liu, Wei Chung Cheng, Hsin Chih Yeh, Chih Pin Chuu, Jen Kun Chen, Bo Ying Bao, Cheng Hsueh Lee, Chien Chih Ke, Yuan Ru Chen, Yun Hsin Yu, Shu Pin Huang, Chia Yang Li

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1019-1039
Number of pages21
JournalAmerican Journal of Chinese Medicine
Volume51
Issue number4
DOIs
StatePublished - 2023
Externally publishedYes

Keywords

  • Akt/mTOR Signaling Pathway
  • Epithelial-Mesenchymal Transition
  • Migration
  • Morusin
  • Prostate Cancer

ASJC Scopus subject areas

  • Complementary and alternative medicine

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