Abstract A53: Apoptosis initiated in colon cancer cells when treated with muscadine grape extract

Abstract

A53 Research suggests strong correlations between the inflammation process and colon cancer progression, making it an attractive target for anti-inflammatory drugs and compounds. Muscadines (Vitis rotundifolia), a grape species native to the Southeastern United States, are rich in polyphenols containing many biologically important flavonoids that may have potential anti-inflammatory and anti-oxidant properties. Current research has shown that the muscadine grape has a higher total phenolic and flavonoid content than commercially available red grapes. A hallmark of progressive colon cancers is disruption of different signaling pathways leading to increased proliferation and escape from apoptotic mechanisms. We hypothesize that extracts containing high levels of biologically important polyphenols from the muscadine pomace would induce cell cycle arrest and apoptosis in HT-29 and HT-15 colon cancer cell lines. Polyphenolic compounds were extracted from muscadine pomace using 80% methanol in 6N hydrochloric acid at 60ºC. Whole concentrated extract (WCE) was fractionized using an Oasis HLB column to yield three different muscadine fractions (MF). We compared the cytotoxic effects of both cell lines when treated with WCE versus three different muscadine fractions (MF-1, MF-2, and MF-3). Cell proliferation assays showed a decrease in viable cell proliferation in both cell lines treated with MF-3. Apoptosis was confirmed through the use of flow cytometry and we found evidence of G1 arrest in MF-3 treated cells. Immunoblots for apoptosis-related proteins suggest apoptotic activation of the caspase-3 pathway in treated cells compared to non-treated cells. We conclude that extracts of muscadine grape contain biologically active polyphenols that inhibit the growth of HT-29 and HT-15 colon cancer cells via an apoptotic pathway. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A53.

The flavokawains: uprising medicinal chalcones

“…Tang et al . [24] suggested that the molecular mechanism underlying this occurrence was through the reduction of inhibitory kinases, Myt1 and Wee1 [24]. In a similar study conducted by Zi et al .…”

“…For instance, in a research conducted by Tang et al . in 2008 [24], flavokawain A affected the cell cycle regulation of a p53-wild-type bladder cancer cell line (RT4). It was found that flavokawain A increased the amount of p21 and p27 cell cycle regulatory proteins and induced a G1 arrest [24].…”

“…in 2008 [24], flavokawain A affected the cell cycle regulation of a p53-wild-type bladder cancer cell line (RT4). It was found that flavokawain A increased the amount of p21 and p27 cell cycle regulatory proteins and induced a G1 arrest [24]. Furthermore, it was discovered that in p53-mutant-type T24 cells, flavokawain A induced a G2/M arrest instead [24].…”

“…It was found that flavokawain A increased the amount of p21 and p27 cell cycle regulatory proteins and induced a G1 arrest [24]. Furthermore, it was discovered that in p53-mutant-type T24 cells, flavokawain A induced a G2/M arrest instead [24]. Tang et al .…”

“…Besides in vitro , analyses on in vivo model were also conducted by some studies [7,24,34]. A research by Tang et al .…”