Methylferulate from Tamarix aucheriana inhibits growth and enhances chemosensitivity of human colorectal cancer cells: possible mechanism of action

Abstract

BackgroundNatural products are valuable sources for anticancer agents. In the present study, methylferulate (MF) was identified for the first time from Tamarix aucheriana. Spectral data were used for identification of MF. The potential of MF to control cell growth, cell cycle, apoptosis, generation of reactive oxygen species (ROS), cancer cell invasion, nuclear factor kappa B (NFkB) DNA-binding activity and proteasomal activities, as well as the enhancement of chemosensitivity in human colorectal cancer cells, were evaluated. The possible molecular mechanism of MF’s therapeutic efficacy was also assessed.MethodsColumn chromatography and spectral data were used for isolation and identification of MF. MTT, immunofluorescence, flow cytometry, in vitro invasion, fluoremetry, EIA and Real time qPCR were used to measure antiproliferative, chemo-sensitizing effects and other biochemical parameters.ResultsMF showed a dose-dependent anti-proliferative effect on colorectal cancer cells (IC50 = 1.73 – 1.9 mM) with a nonsignificant cytotoxicity toward normal human fibroblast. Colony formation inhibition (P ≤ 0.001, 0.0001) confirmed the growth inhibition by MF. MF arrested cell cycle progression in the S and G2/M phases; induced apoptosis and ROS generation; and inhibited NF-kB DNA-binding activity, proteasomal activities and cell invasion in colorectal cancer cells. MF up-regulated cyclin-dependent kinase inhibitors (p19 INK4D, p21WAF1/CIP1, p27KIP1), pro-apoptotic gene expression (Bax, Bad, Apaf1, Bid, Bim, Smac) and caspases (caspase 2, 3, 6, 7, 8, 9). Moreover, MF down-regulated cyclin-dependent kinases (Cdk1, Cdk2) and anti-apoptotic gene expression (c-IAP-1, c-IAP-2, Bcl2,FLIP). In addition, MF differentially potentiated the sensitivity of colorectal cancer cells to standard chemotherapeutic drugs.ConclusionMF showed a multifaceted anti-proliferative and chemosensitizing effects. These results suggest the chemotherapeutic and co-adjuvant potential of MF.

Anticancer, Cytotoxic Effect of Tamarix Aphylla, and Antibacterial Screening Efficiency Against Multidrug-Resistant Human Pathogens

“…Medicinal plant possesses that anticancer activity is regarded as one of the most attractives to explore natural anticancer agent for cancer control since certain natural compounds present in medicinal plants have efficiently inhibited tumor development in various human organs [33,34]. Another study showed that methyl ferulate from Tamarix aucheriana inhibits growth and enhances chemosensitivity of human colorectal cancer cells [12]. Antiproliferative of T. aphylla leaf extracts showed better cytotoxicity activity against MCF-7 cells, and therefore, it will be used for further antiproliferative investigation.…”

“…Currently, 50% of all drugs in the market and 74% of the most important drugs are derived from phytochemicals [9,11]. Currently, more than 60% of commercially available anticancer drugs are derived from natural sources, including plants, marine organisms, and microorganisms [9,12]. To date, more than 3000 different plant species have been used in the treatment of different types of cancer [9,11].…”

“…To date, more than 3000 different plant species have been used in the treatment of different types of cancer [9,11]. Extensive research on medicinal plants has identified several botanical natural compounds that have chemopreventive potential [12]. Plant bioactive molecules and phytochemicals could prevent more 20% of cases of cancer and may potentially prevent approximately 200,000 cancer-related deaths annually.…”

Osterix Decreases the Chemosensitivity of Breast Cancer Cells by Upregulating GALNT14

“…The induction of apoptosis in cancer cells is expedient in the prevention of cancer [37]. Cancer cells possess the ability to evade apoptosis, rendering cytotoxic drugs ineffective, an activity that is considered one of the challenges in cancer treatment.…”

Water Extract of Tamarix gallica L. as effective Agents against C6 and HeLa tumor cell lines

“…All rights reserved colorectal cancer cells, were evaluated. The possible molecular mechanism of MF's therapeutic efficacy was also assessed [25].…”