Pro-oxidant Tetrapleura tetraptera polyphenol extract parallels quercetin as an in vitro cytotoxic agent in human liver cancer cells

Abstract

Tetrapleura tetraptera (TT) fruits, also called aidan fruits, are traditionally used in Africa and other parts of the world as a spice in foods and in treating diseases such as arthritis, diabetes, infections and cardiovascular diseases but have remained largely underutilized. To find new ways of utilizing TT dry fruits, this study produced pro-oxidant polyphenols from it by applying the combined effects of high-power, low frequency ultrasound and the Fenton-like mechanism. The efficacy of the pro-oxidant polyphenols as cytotoxic agent was tested in human liver cancer cells (HepG2), evaluating its potential use as an anti-cancer remedy. The Folin Ciocalteau, DPPH, ABTS and cellular antioxidant activity (CAA) assays were used to determine total phenolic content (TPC) and antioxidant property of extracts. Pro-oxidant property of extracts was confirmed using lipid oxidation assays that measured malondialdehyde (MDA) levels and peroxide value (PV) in samples. It was found that TT polyphenol (TTP) extract treated with FeCl3 (TTP-FeCl3) showed poor antioxidant properties evident in its ability to promote lipid oxidation (i.e. increasing MDA levels from 0.17 to 2.53 µmol g−1 and PV from 0.40 to 1.16 meq O2 kg−1 fat). It also induced cytotoxic effects in HepG2 cells. From LC-ESI-MS analysis, the major phenolic compounds and their concentrations in the TTP-FeCl3 extract were kaempferol-3-O-rutinoside (23.75 µg g−1), 4-O-methylgallic acid (19.05 µg g−1), chlorogenic acid (16.22 µg g−1), rutin (16.15 µg g−1), quercetin-3-O-glucuronide (13.19 µg g−1), cyanidin-3-O-galactoside (12.58 µg g−1), orientin (10.99 µg g−1), isorhamnetin-3-O-glucoside (10.11 µg g−1) and gallic acid (10.47 µg g−1). This study showed that prolonged high-power, low-frequency ultrasonication in combination with FeCl3 treatment can be used to produce pro-oxidant polyphenols capable of eliciting cytotoxic effects in HepG2 cells in vitro. Exploring targeted delivery of TTP pro-oxidants with cytotoxic properties has great potential in disease management.