Next Article in Journal
Enhanced Immune Response Against the Thomsen-Friedenreich Tumor Antigen Using a Bivalent Entirely Carbohydrate Conjugate
Next Article in Special Issue
Norhierridin B, a New Hierridin B-Based Hydroquinone with Improved Antiproliferative Activity
Previous Article in Journal
Prediction Model of Aryl Hydrocarbon Receptor Activation by a Novel QSAR Approach, DeepSnap–Deep Learning
Previous Article in Special Issue
Anticancer Potential of Raddeanin A, a Natural Triterpenoid Isolated from Anemone raddeana Regel
Open AccessArticle

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

1
Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
2
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh -11451, Saudi Arabia
3
Narula Research, Chapel Hill, NC 27516, USA
4
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; https://doi.org/10.3390/molecules25061320
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
Show Figures

Figure 1

MDPI and ACS Style

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.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop