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Open AccessArticle

Evodiamine Mitigates Cellular Growth and Promotes Apoptosis by Targeting the c-Met Pathway in Prostate Cancer Cells

Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh -11451, Saudi Arabia
Narula Research, Chapel Hill, NC 27516, USA
Center for Drug Discovery, RTI International, Research Triangle Park, Durham, NC 27709, USA
Author to whom correspondence should be addressed.
Molecules 2020, 25(6), 1320;
Received: 22 February 2020 / Accepted: 11 March 2020 / Published: 13 March 2020
(This article belongs to the Special Issue Nature-Inspired Antitumor Agents )
Evodiamine (EVO) is an indoloquinazoline alkaloid that exerts its various anti-oncogenic actions by blocking phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), mitogen-activated protein kinase (MAPK), c-Met, and nuclear factor kappa B (NF-κB) signaling pathways, thus leading to apoptosis of tumor cells. We investigated the ability of EVO to affect hepatocyte growth factor (HGF)-induced c-Met/Src/STAT3 activation cascades in castration-resistant prostate cancer (CRPC). First, we noted that EVO showed cytotoxicity and anti-proliferation activities in PC-3 and DU145 cells. Next, we found that EVO markedly inhibited HGF-induced c-Met/Src/STAT3 phosphorylation and impaired the nuclear translocation of STAT3 protein. Then, we noted that EVO arrested the cell cycle, caused apoptosis, and downregulated the expression of various carcinogenic markers such as B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), cyclin D1, cyclooxygenase 2 (COX-2), survivin, vascular endothelial growth factor (VEGF), and matrix metallopeptidases 9 (MMP-9). Moreover, it was observed that in cPC-3 and DU145 cells transfected with c-Met small interfering RNA (siRNA), Src/STAT3 activation was also mitigated and led to a decrease in EVO-induced apoptotic cell death. According to our results, EVO can abrogate the activation of the c-Met/Src/STAT3 signaling axis and thus plays a role as a robust suppressor of tumor cell survival, proliferation, and angiogenesis. View Full-Text
Keywords: evodiamine; c-Met; STAT3; prostate cancer; apoptosis evodiamine; c-Met; STAT3; prostate cancer; apoptosis
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Hwang, S.T.; Um, J.-Y.; Chinnathambi, A.; Alharbi, S.A.; Narula, A.S.; Namjoshi, O.A.; Blough, B.E.; Ahn, K.S. Evodiamine Mitigates Cellular Growth and Promotes Apoptosis by Targeting the c-Met Pathway in Prostate Cancer Cells. Molecules 2020, 25, 1320.

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