Standardized Pluchea Indica Leaf Extract Exhibited Antiproliferative Activity Against TGF-β-induced Prostate Stromal Cells (WPMY-1) Through G 1 Phase Cell Cycle Arrest via SMAD2/3 and ERK1/2 Signaling Pathways

标准化印度番荔枝叶提取物通过SMAD2/3和ERK1/2信号通路阻滞G1期细胞周期,对TGF-β诱导的前列腺基质细胞(WPMY-1)表现出抗增殖活性。

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作者:Yanisa Kanphet ,Tamonwan Uttarawichien ,Boonyadist Vongsak ,Teerawat Boonsom ,Nonthaneth Nalinratana ,Sathiyaraj Sivaji ,Pasarapa Towiwat ,Suchada Sukrong

Abstract

Background/aim: Benign prostatic hyperplasia (BPH) is characterized by the abnormal proliferation of prostate stromal cells, resulting in the enlargement of the prostate gland and the manifestation of troublesome symptoms, such as nocturia, urinary retention, and urinary incontinence. Dihydrotestosterone (DHT) and interleukin-17 (IL-17) are known to be key factors in promoting the overproduction of transforming growth factor-beta (TGF-β) in prostate stromal cells, contributing to their excessive proliferation, leading to BPH. Materials and methods: In this study, selected plant extracts traditionally used to alleviate urinary symptoms were subjected to primary screening for their anti-proliferative activity by evaluating DHT- and IL-17-induced proliferation in WPMY-1 prostate stromal cells. This was followed by a secondary screening using TGF-β induction. Results: The extract that significantly inhibited cell proliferation was standardized and further investigated for its anti-proliferative effects through the TGF-β signaling pathway. Results showed that the leaf extract of P. indica significantly inhibited cell proliferation induced by DHT, IL-17, and TGF-β. It was demonstrated that P. indica has anti-proliferative properties via the TGF-β signaling pathways by inhibiting PCNA protein expression and inducing cell accumulation at the G0/G1 phase, while reducing the cell population at the S phase. Additionally, it down-regulated the expression of both canonical (p-SMAD2/3) and non-canonical (p-ERK1/2) proteins in TGF-β-induced WPMY-1 cells. Conclusion: The standardized leaf extract of P. indica showed notable anti-proliferative activity against TGF-β-induced WPMY-1 cells by arresting the cell cycle at the G0/G1 phase through the SMAD2/3 and ERK1/2 signaling pathways.

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