cis-Terpenones as an Effective Chemopreventive Agent against Aflatoxin B1-Induced Cytotoxicity and TCDD-Induced P450 1A/B Activity in HepG2 Cells

Abstract

Aflatoxin B1 (AFB1) is a potent carcinogen, which can significantly increase the risk of hepatocellular carcinoma development through food contamination. In past decades, chemopreventive agents such as oltipraz and chlorophyllins have demonstrated that chemointervention is an effective approach to reduce the hepatotoxicity by AFB1. However, due to the potential adverse effects of these agents, alternative novel mechanism-based chemopreventive agents are needed. We report here that novel cis-terpenones 1-3, which were synthesized as the precursors of natural product analogues in our laboratory, showed promising protective effects against AFB1 induced cytotoxicity in HepG2 cells. Chemo-protection was observed with increasing concentrations of cis-terpenones in the co-treatment of AFB1, and no cytotoxicity was observed with cis-terpenones alone. In addition, cis-terpenones 1-3 at 10 μM effectively inhibited induced cytochrome P450 1A/ 1B activity by 50% in HepG2 cells, as indicated by an EROD assay. P450 1A/B is involved in the activation of many pre-carcinogens and is highly inducible in liver cells. These results suggested that novel terpenones 1-3 are candidates for the development of novel mechanism-based chemopreventive agents against AFB1 and other carcinogenic stimuli.

The effect of <i>Hibiscus sabdarriffa</i> calyx extraction cisplatin-induced tissue damage in rats

“…The extract may also reduce the involvement of Ca 2+ dependent permeabilisation of renal cortex mitochondria as it has been shown that there is a possible involvement of Ca 2+ dependent permeabilisation of renal cortex mitochondria in cisplatin nephrotoxicity 19 . Anthocyanins are ubiquitous in the calyces of the plant thus this property of the extract may be attributed partly to these flavonoids which are known to be potent antioxidants and free radical scavengers 25 .…”

“…Further work should focus on elucidating the actual protective mode of the extract. Since there are various phytochemicals in the calyces, proper fractionation of the extract should be done and each fraction subjected to both in vitro and in vivo studies since some notable bioactivities of terpenes have also been reported 25 in addition to the fact that flavonoids also possess pro-oxidant activities 26 . Progress in this area will also extend the borders of even cisplatin chemotherapy.…”

Antimalarial activity of a cis-terpenone

“…OHCT, like artemisinin, rapidly kills the early ring stage in vitro , suggesting that it could be used in combination with a slow-acting drug, such as chloroquine. The previous demonstrations that OHCT inhibits human liver cytochrome P450 3A4 [ 8 , 9 ] further suggests that it may reduce metabolism of anti-malarial compounds, such as artemisinin, that are metabolized by this enzyme [ 11 ], thus increasing the half-life and rendering them more effective. The inhibition of human liver cytochrome P450 3A4 by OHCT was shown to be mixed competitive inhibition indicating that OHCT was binding at a site different from the active site [ 9 ].…”

“…Synthesis of HCT and OHCT was described previously [ 7 , 8 ]. It was previously shown that OHCT protects human liver cells against aflatoxin and inhibits activity of liver microsomal cytochrome P450 3A4 [ 9 ].…”

Antioxidant activities of Solenostemon monostachyus leaf extract using in vitro methods

“…Examples are the terpenoids β-pinene, oct-1-en-3-ol, β-caryophyllene, octan-3-ol, and E, E-αfarnesene ( Figure 2) (Eyele et al, 2006). Dietary polyphenols, carotenoids and terpenes have exhibited significant medicinal potentials (Wang et al, 2008;Zhou et al, 2006). The observed effects of S. monostachyus could be ascribed to these antioxidant phytochemicals which acted in synergy.…”