Growth inhibition and apoptosis in cancer cells induced by polyphenolic compounds of Acacia hydaspica: Involvement of multiple signal transduction pathways

Abstract

Acacia hydaspica R. Parker is known for its medicinal uses in multiple ailments. In this study, we performed bioassay-guided fractionation of cytotoxic compounds from A. hydaspica and investigated their effects on growth and signaling activity in prostate and breast cancer cell lines. Four active polyphenolic compounds were identified as 7-O-galloyl catechin (GC), catechin (C), methyl gallate (MG), and catechin-3-O-gallate (CG). The four compounds inhibited prostate cancer PC-3 cell growth in a dose-dependent manner, whereas CG and MG inhibited breast cancer MDA-MB-231 cell growth. All tested compounds inhibited cell survival and colony growth in both cell lines, and there was evidence of chromatin condensation, cell shrinkage and apoptotic bodies. Further, acridine orange, ethidium bromide, propidium iodide and DAPI staining demonstrated that cell death occurred partly via apoptosis in both PC-3 and MDA-MB-231 cells. In PC-3 cells treatment repressed the expression of anti-apoptotic molecules Bcl-2, Bcl-xL and survivin, coupled with down-regulation of signaling pathways AKT, NFκB, ERK1/2 and JAK/STAT. In MDA-MB-231 cells, treatment induced reduction of CK2α, Bcl-xL, survivin and xIAP protein expression along with suppression of NFκB, JAK/STAT and PI3K pathways. Our findings suggest that certain polyphenolic compounds derived from A. hydaspica may be promising chemopreventive/therapeutic candidates against cancer.

Hepatoprotective potential of Fagonia olivieri DC. against acetaminophen induced toxicity in rat

“…The antioxidants such as polyphenolics can protect the biological systems against the harmful effects of oxidative processes [4]. Thus, increased consumption of plant derived products which are good sources of antioxidants is a convenient way to control the diseases induced with oxidative stress [5]. …”

“…Antioxidants can be of synthetic origin and can be a great number of secondary metabolites isolated from plants, such as various phenolic compounds [5]. Synthetic antioxidants like butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) were found to have genotoxic effect [6].…”

Design, Synthesis, and Biological Evaluation of 2‐(2‐Bromo‐3‐nitrophenyl)‐5‐phenyl‐1,3,4‐oxadiazole Derivatives as Possible Anti‐Breast Cancer Agents

“…Once the cells were attached, and morphology was clear, cells were treated with different concentrations (1, 3, 10, 100 μ m ) of test drug and were kept under incubation (37 °C, 5 % CO 2 ) for 48 h. After 48 h, the culture media were removed, and cells were washed with PBS. AO/EtBr staining was performed at a concentration of 100 μg/ml AO (100 μl) and 100 μg/ml EtBr (100 μl) and cells were visualized immediately under fluorescence microscope at λ exe 460 nm and maximum λ emi of 650 nm …”

“…AO/EtBr staining was performed at a concentration of 100 μg/ml AO (100 μl) and 100 μg/ml EtBr (100 μl) and cells were visualized immediately under fluorescence microscope at λ exe 460 nm and maximum λ emi of 650 nm. [37,38] Enzyme Inhibitor Assay of DNA Methyl Transferase DNA methylation is an essential indicator of human cancer for silencing tumor-suppressing the genes and has an equivalent significance to classic genetic mutations. [39] Eight isoforms of DNA methyltransferases (DNMT) were identified, and among them, three isoforms were focused on much.…”

Anti-Prostate Cancer Activity of Plant-Derived Bioactive Compounds: a Review

“…Methanolic extracts of the bark, twigs, and leaves of Acacia hydaspica contains polyphenolic compounds-7-O-galloyl catechin, catechin, methyl gallate, and catechin-3-O-gallate. These phytochemicals repressed the expression of anti-apoptotic molecules, and inhibited the proliferation, in PC-3 cells [26]. Similarly, extracts from the leaves and stems of Dalea frutescens, which contain chalconessanjuanolide and sanjoseolide, are anti-proliferative and cytotoxic to PC-3 and DU145 cells [27].…”