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.
Highlights
The increased understanding of cellular signaling pathways known to be deregulated in cancer has resulted in considerable progress in generation of targeted therapies
Flavonoids have been demonstrated to exert their effects on a variety of biological functions including inhibiting the cell cycle, reducing oxidative stress, augmenting the efficacy of detoxification enzymes, inducing apoptosis, and stimulating the immune system
We have attempted to study the mechanism of action of the flavanols isolated from A. hydaspica on human androgen-independent prostate cancer (PC-3) and triple negative breast cancer (MDA-MB-231) cell lines as models
Summary
The increased understanding of cellular signaling pathways known to be deregulated in cancer has resulted in considerable progress in generation of targeted therapies. Considerable effort has centered around identifying agents present in diets or other plants that could serve as chemopreventive or chemotherapeutic agents for various type of diseases including cancer with the advantage that they may have minimal or no unwanted toxicity (see, e.g.,7–11) Along these lines, one of the first studies demonstrated the activity of polyphenolic compound EGCG (epigallocatechin-3-gallate) present in green tea extract to influence the growth of various cancers as well as its chemopreventive properties[11]. Compounds identified from Acacia species are known to modulate various signaling pathways in breast and prostate cancer[18,19] These studies have generally utilized the total extracts from various catechin sources reflecting effects of combined activities of several compounds rather than of a single compound. The results provide, for the first time, evidence that A. hydaspica compounds (AHCs) could potentially serve as chemopreventive/therapeutic agents against cancer
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