Phloridzin fatty acid esters induce apoptosis and alters gene expression in human liver cancer cells (261.2)

Abstract

Phloridzin Fatty Acid Esters Induce Apoptosis and Alters Gene Expression in Human Liver Cancer Cells Sandhya VG Nair, Ziaullah, HP Vasantha Rupasinghe*Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada Abstract Phloridzin (phloretin 2‐O‐glucoside) is a dihydrochalcone, which is specifically found in apple and well known for its beneficial biological effects. To date, there is no report of antiproliferative effect of phloridzin on human cancer cell lines. We have synthesized novel acylated derivatives of phloridzin with six different long chain saturated, mono‐, and poly‐unsaturated fatty acids by regioselective enzymatic acylation. We investigated the effect of these six phloridzin fatty acid esters and their parent compounds on cell proliferation of hepatocellular carcinoma cells (HepG2) and its potential molecular mechanisms. Phloridzin fatty acid esters inhibited HepG2 cells growth in a concentration‐dependent manner by inducing apoptosis, as evidenced by decreased cell viability, formation of apoptotic bodies, decreased mitochondrial membrane potential, activation of caspase 3 and inhibition of DNA topoisomerases IIα activity that might induce G0/G1 phase arrest. However, phloridzin fatty acid esters did not significantly affect the growth of normal hepatocytes. Antiproliferative effect of phloridzin docosahexaenoic acid (DHA) ester was also associated with the down regulation of anti‐apoptotic genes, growth factor receptors, PI3k/AKT/mTOR as well as epigenetics regulators. Results reveal that phloridzin fatty acid esters possess potential as therapeutic agents for treating hepatocellular carcinoma.

Attempts to Create Products with Increased Health-Promoting Potential Starting with Pinot Noir Pomace: Investigations on the Process and Its Methods

“…The production of lipophilic flavonoids and their improved activity against these two cell lines (compared to that of their parent compounds) have previously been exemplified in the literature. For example, Omonga et al demonstrated that O-alkyl derivatives of chrysin increased activity against HCT116; whilst Nair et al demonstrated fatty esters of phloridzin increased the inhibitory effects against MDA-MB-231 [61,62]. Further, our group also found that lauroyl, octanoyl and palmitoyl derivatives of quercetin and luteolin had the greatest improvements against these two cell lines.…”

Phloridzin Docosahexaenoate Inhibits Spheroid Formation by Breast Cancer Stem Cells and Exhibits Cytotoxic Effects against Paclitaxel-Resistant Triple Negative Breast Cancer Cells

“…PZ-DHA is a fatty acid ester of PZ (Figure 1) [20] formed through an acylation reaction. Of the six fatty acid esters tested, PZ-DHA was the most effective chemotherapeutic agent [21]. ceptors that TNBCs lack.…”

“…PZ-DHA is a fatty acid ester of PZ (Figure 1) [20] formed through an acylation reaction. Of the six fatty acid esters tested, PZ-DHA was the most effective chemotherapeutic agent [21]. Treatment with PZ-DHA significantly downregulates the expression of cancerpromoting genes in HepG2 cells, while having little cytotoxic effect on normal human and rat hepatocytes [21].…”

“…Of the six fatty acid esters tested, PZ-DHA was the most effective chemotherapeutic agent [21]. Treatment with PZ-DHA significantly downregulates the expression of cancerpromoting genes in HepG2 cells, while having little cytotoxic effect on normal human and rat hepatocytes [21]. Furthermore, PZ-DHA inhibits the growth of three forms of leukemia cells, namely THP1, K562, and Jurkat, in vitro [20,22].…”

“…Furthermore, PZ-DHA inhibits the growth of three forms of leukemia cells, namely THP1, K562, and Jurkat, in vitro [20,22]. PZ-DHA also has a selective cytotoxic effect on breast cancer cells in vitro and in vivo (MDA-MB-231, MDA- Treatment with PZ-DHA significantly downregulates the expression of cancer-promoting genes in HepG2 cells, while having little cytotoxic effect on normal human and rat hepatocytes [21]. Furthermore, PZ-DHA inhibits the growth of three forms of leukemia cells, namely THP1, K562, and Jurkat, in vitro [20,22].…”