Proanthocyanidins reduce cellular function in the most globally diagnosed cancers in vitro

Abstract

Background Growing evidence indicates that proanthocyanidins (PACs) may be effective in treating and preventing various cancers. The fundamental mechanism of PACs inhibiting the proliferation at cellular and molecular levels in most of the cancer types remains unclear. Objective The anticancer efficacy of PACs was investigated in vitro using three human cancer cell lines: human colorectal adenocarcinoma (HT-29), human breast carcinoma (MCF-7), and human prostatic adenocarcinoma (PC-3). Methods Cytotoxicity was evaluated by MTT assay, while cell proliferation was measured by trypan blue exclusion method. Cell migration was measured by wound healing assay, and DAPI staining was used to evaluate apoptotic nucleus morphology. RT-PCR was used to analyze the expression of Bax and Bcl-2, and caspase enzyme activity assay was measured by caspase colorimetric assay. Results PACs could inhibit both cellular viability and proliferation in a concentration- and time-dependent fashion in all investigated cells. Further, all tested cells showed similarly decreased migration after 24- and 48-h PAC treatment. We observed increased apoptotic nucleus morphology in treated cells (p ≤ 0.01). BAX expression significantly increased in HT-29 (p < 0.01), PC-3(p < 0.01), and MCF-7 (p < 0.05) cells, while BCL-2 expression significantly declined (p < 0.05). Caspase activities were significantly increased in all tested cancer cell lines after 24-h PAC treatment. Conclusion PACs may have potential therapeutic properties against colorectal, breast, and prostate cancer.

Anti-Proliferative and Pro-Apoptotic Effects of Digested Aglianico Grape Pomace Extract in Human Colorectal Cancer Cells

“…Similar results were found following the exposure of HT29 cells to other types of flavonols—hyperoside and rutin—abundant in wine, grapes, and citrus fruits [ 34 ], showing an increase in Bax expression, a reduction in Bcl-2, and an increase in Bax/Bcl-2 in a dose-dependent manner [ 35 ]. Furthermore, our results were also supported by a recent study performed on HT29, MCF-7, and PC-3 cells treated with proanthocyanidins for 24 h and 48 h [ 26 ], highlighting a significant increase and decrease in Bax and Bcl-2, respectively. In addition, Reddivari et al [ 36 ] have shown that a bioactive compound of grapes, in particular resveratrol, together with grape seed extract, induced apoptosis in colon cancer stem cells.…”

“…Similarly, the polyphenols extract inhibited the HT29 cell proliferation, with a significant decrease at 80 μg/mL (0.74 ± 0.01). Previous scientific studies reported that HT29 cells exposed to an increasing concentration of proanthocyanins inhibited the cell proliferation after 24 h of treatment [ 26 ]. Moreover, pomegranate polyphenols have also been demonstrated to decrease cell proliferation on colon rectal cancer cells by inducing apoptosis [ 27 ].…”

Oligomeric proanthocyanidin grape seed extracts inhibited oncogenic signaling crosstalk of ERK1/2, β-catenin, and STAT3 through apoptosis induction in human liver and breast cancer cell lines.

“…Others have indicated that the process of apoptosis is integrated with the overexpression of pro-survival genes, like some of the BCL-2 family members, and proapoptotic genes, like Bax, that have a central role in the regulation of the apoptotic process. Bax overexpression triggers the cells to enter the apoptosis stage, causing increased caspase-3 (40). The present study led to a possible mechanistic part of extracted OPC-PACs on apoptosis induction linked to a significant increase of nuclear apoptosis, caspase-3 increased activities, and Bax up-regulation linked to the substantial inhibition of the oncogenic signal's crosstalk.…”

“…It was reported on the IC 50 values of OPC-PACs on three cancer cell lines that showed significant induction of cell cytotoxicity in a concentration and time-dependent manner. The published data of human prostatic adenocarcinoma (PC-3), human colorectal adenocarcinoma (HT-29), and human breast carcinoma (MCF-7) cell lines showed that different concentration OPC-PACs extracts inhibited cell viability and proliferation detected by cell cytotoxicity after 24 and 48 h. (40).…”