Tamarix Articulata Exhibits Antiproliferative and Antimetastatic Activity by Modulating PI3K-Akt and TGF-β-Mediated Downstream Signaling in Prostate Cancer Cells

Abstract

Anticancer drugs mainly kill tumor cells through the apoptosis mechanism, but they can become ineffective when tumor cells are metastatic. Thus, searching for plant-based extracts/compounds to curtail metastasis is extremely important. This study aims to evaluate the anticancer potential of Tamarix articulata (TA) extract against prostate cancer cells. MTT, Brd U, and trypan blue assays was performed to evaluate the cell viability. TUNEL assay were performed to determine apoptotic cells. Clonogenic, wound healing and Boyden chamber assay were conducted to evaluate the anti-clonogenic, anti-motility, and anti-invasive potential of TA. Zymography and immunoblotting were done to check the activity and expression of metalloproteases and proteins associated with metastasis. Our results demonstrated that TA extract significantly inhibits cell viability, clonogenic property, and displays IC₅₀ values in the 245–289 µg/mL range. TA extract significantly abrogates the motility and invasive property of LnCaP cells in a dose-dependent manner. Mechanistically, TA extract downregulates the expression of PI3K-Akt/TGF-β-SMAD2/3 and MMP-2/-9 with concomitant upregulation of TIMP1 expression in LnCaP cells. Additionally, we observe a dose-dependent downregulation of snail and vimentin with the upregulation of E-cadherin protein expression in LnCaP cells. In conclusions, TA extract exhibits an antiproliferative effect, abrogates cell motility and invasion by downregulating PI3K-Akt/TGF-β-SMAD2/3, MMP-2/9, snail, and vimentin with concomitant upregulation of E-cadherin and TIMP1 expression in prostate cancer cells.

keywords: Molecular Biology, Tamarix articulata, plant extracts, metastasis, anticancer, prostate cancer, apoptosis, cell motility, cell invasion