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.

Evaluating anticancer properties of Withaferin A—a potent phytochemical

“…Induction of ER stress is noted in colorectal cancer (CRC) cells in a combination treatment of Withaferin A and 5-Fluorouracil resulting in autophagy and apoptosis was observed (Alnuqaydan et al, 2020). Furthermore, PCR analysis revealed an increased mRNA expression of BiP, CHOP, PERK, and eIF2α, which are ER stress markers, in CRC cells upon exposure to combination treatment of Withaferin A and 5-Fluorouracil (Alnuqaydan et al, 2020).…”

“…Synergistic effects of Withaferin A and 5-fluorouracil have been observed in a study involving colorectal cancer (CRC) cells where the combination treatment of the two substances leads to antiproliferation of the cells and induces endoplasmic reticulum (ER) stress, resulting in apoptosis and autophagy (Alnuqaydan et al, 2020). The antiproliferative potential of combination treatment was observed as the CRC cells were exposed to 0.1-100 µM of Withaferin A and 5-Fluorouracil resulting in reduction in cell viability in dose dependent manner (Alnuqaydan et al, 2020). The same study also revealed attenuation of expression of proteins associated with β-catenin pathway and cell cycle arrest in G2/M phase in colorectal cancer (CRC) cells (Alnuqaydan et al, 2020).…”

“…The antiproliferative potential of combination treatment was observed as the CRC cells were exposed to 0.1-100 µM of Withaferin A and 5-Fluorouracil resulting in reduction in cell viability in dose dependent manner (Alnuqaydan et al, 2020). The same study also revealed attenuation of expression of proteins associated with β-catenin pathway and cell cycle arrest in G2/M phase in colorectal cancer (CRC) cells (Alnuqaydan et al, 2020). Higher IC 50 values of both compounds in normal colon cells was noted in comparison to CRC cells indicating a safe toxicity profile at a concentration where antiproliferative effects are observed (Alnuqaydan et al, 2020).…”

“…Higher IC 50 values of both compounds in normal colon cells was noted in comparison to CRC cells indicating a safe toxicity profile at a concentration where antiproliferative effects are observed (Alnuqaydan et al, 2020). The effects of combination treatment of Withaferin A and 5-flurouracil are of crucial importance as the currently available 5-flurouracil treatment is of concern due to its toxicity (Alnuqaydan et al, 2020).…”