The Molecular Mechanisms of Apoptosis Induced by A llium flavum  L. and Synergistic Effects with New-Synthesized Pd(II) Complex on Colon Cancer Cells

Abstract

Considering that induction of apoptosis is one of the main strategies in cancer therapy, the molecular mechanisms of cytotoxic effects of Allium flavum L. on colon cancer cell lines were investigated and applied in single and co-treatments with new-synthesized Pd(II) complex. The analysis of chemical composition identified caffeic acid glycosides as the most dominant phenolics in A. flavum extract. In all investigated extracts, A. flavum showed cytotoxic effects on colon cancer cells (IC50 = 1.64-84 μg/mL) but not on healthy cells. Combinations of plant extracts with Pd(II) complex caused lower IC50 values and better proapoptotic activity. Pd(II) complex induced high percentage of necrosis in a single treatment, but in the combination with plant extracts it had better proapoptotic and lower necrotic activity. Treatments and co-treatments induced higher O2 − production and influenced apoptosis biomarkers, leading to Fas protein overexpression and activation of caspases 8 and 9.

Altered apoptosis and biotransformation signaling in HCT-116 colorectal carcinoma cells induced by Teucrium chamaedrys L. extract

“…The voucher specimen of T. chamaedrys has been deposited with the number 16695 at the Herbarium of the Faculty of Biology, University of Belgrade, Serbia. Methanol extract was prepared according to standard procedure, formerly described (MILUTINOVIĆ et al, 2015). Stock solution of crude plant extract was prepared in DMSO (Dimethyl sulfoxide), where the highest concentration of DMSO used for final dilution of extracts did not exceed 0.5%.…”

“…Human colorectal carcinoma cell line (HCT-116) was obtained from American Type Culture Collection. The cells were maintained in optimum conditions and standard protocols (MILUTINOVIĆ et al, 2015). All assays were performed 24 h after treatment with T. chamaedrys extract, in concentration of 50 µg/ml, and nontreated cells were used as control.…”

“…Measuring of activity of caspase 8 and 9 was performed by colorimetric assay kits (RD Systems), according to the manufacturer's protocols, as formerly described in detail (MILUTINOVIĆ et al, 2015).…”

“…There is a wide number of medicinal plants, plant-derived products or isolated compounds, mainly polyphenols, with significant anticancer activity (BISHAYEE, 2012;FRIDLENDER et al, 2015). Their anticancer properties are mediated through different mechanisms including interaction with DNA repair systems, stimulation of immune system, antiproliferative activity on cancer cells, induction of apoptosis, alteration to metabolism of anticancer drug and impact on progressive stages of carcinogenesis by suppression of angiogenesis and metastasis (MILUTINOVIĆ et al, 2015;MANURE and NAIKWADE, 2018). Among these processes, apoptosis has a preventive role as an event in transformed cells during the process of carcinogenesis, as well as a primary mode of action and desirable type of cell death induced in anticancer therapy (PFEFFER and SINGH, 2018).…”

“…Among these processes, apoptosis has a preventive role as an event in transformed cells during the process of carcinogenesis, as well as a primary mode of action and desirable type of cell death induced in anticancer therapy (PFEFFER and SINGH, 2018). A number of crude plant extracts and their constituents induce apoptosis in cancer cells (GALI-MUHTASIB et al, 2015;MILUTINOVIĆ et al, 2015). It can be induced through extrinsic and/or intrinsic pathway, wherein the first includes interaction of death receptors and followed activated molecules, while the intrinsic mainly include mitochondria and molecules associated with changes in permeability of mitochondrial membrane, releasing of cytochrome c, which stimulates appropriate apoptotic molecules (PFEFFER and SINGH, 2018).…”