Ellagic acid inhibits proliferation and induced apoptosis via the Akt signaling pathway in HCT-15 colon adenocarcinoma cells

Abstract

Chemoprevention is regarded as one of the most promising and realistic approaches in the prevention of human cancer. Ellagic acid (EA) has been known for its chemopreventive activity against various cancers and numerous investigations have shown its apoptotic activity both in vivo and in vitro. The present study was focused to elucidate the anticancerous effect and the mode of action of EA against HCT-15 colon adenocarcinoma cells. Cell viability was assessed using trypan blue assay at different concentrations. EA also promoted cell cycle arrest substantially at G2/M phase in HCT-15 cells. The activities of alkaline phosphatase and lactate dehydrogenase were decreased upon EA treatment, which shows the antiproliferative and the cytotoxic effects, respectively. The production of reactive oxygen intermediates, which were examined by 2,7-dichlorodihydrofluorescein diacetate (H2DCF-DA), increased with time, after treatment with EA. In further studies, EA inhibited proliferation-associated markers proliferating cell nuclear antigen and cyclin D1. The induction of apoptosis was accompanied by a strong inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway by EA. The expression of PI3K and pAkt was down-regulated in EA-treated cells, compared to normal cells. Further, EA promoted the expression of Bax, caspase-3, and cytochrome c, and suppression of Bcl-2 activity in HCT-15 cells that was determined by western blot analysis. Increased annexin V apoptotic cells and DNA fragmentation also accompanied EA-induced apoptosis. In conclusion, EA increased the production of ROS, decreased cell proliferation, and induced apoptosis in HCT-15 cells, and thus can be used as an agent against colon cancer.

Honey and its Phytochemicals: Plausible Agents in Combating Colon Cancer through its Diversified Actions

“…Bax expression and caspase-3 activation was noted after ellagic acid supplementation leading to elevation of cytochrome c (cyt c) levels and finally cell death. Following this the effect of ellagic acid on HCT-15 colon cancer cells was found (Umesalma et al 2015). Ellagic acid treatment decreased the cell viability and caused cell cycle arrest at G2/ M phase in the HCT-15 cells.…”

“…Following this the effect of ellagic acid on HCT‐15 colon cancer cells was found (Umesalma et al . ). Ellagic acid treatment decreased the cell viability and caused cell cycle arrest at G2/M phase in the HCT‐15 cells.…”

Ellagic acid, extracted from Sanguisorba officinalis, induces G1 arrest by modulating PTEN activity in B16F10 melanoma cells

“…AKT and MAPK pathways, which play important roles in promoting cell growth and survival, are often abnormally activated in melanoma cells through N-RAS, BRAF and PTEN mutations (Jakob et al, 2012;Luo & Shen, 2017;Zebary et al, 2013). Moreover, other studies indicated that EA is related to the modulation of the AKT and MAPK signaling networks (Kowshik et al, 2014;Umesalma, Nagendraprabhu, & Sudhandiran, 2015). Also, EA increases p53 protein levels in some cancer cell lines (Li et al, 2005).…”

Honey and Cancer: Current Status and Future Directions

“…In cervical cancer cell lines apoptosis was induced at concentrations as low as 20 µM, whereas a higher concentration range (80–100 µM) was required to significantly inhibit apoptosis in bladder, ovarian, and breast cancer cell lines. Ellagic acid is another important flavonoid found in honey and is a potent inducer of apoptosis in cancer cells [86,87,88]. This is, however, being extensively covered in another review in this issue.…”