Inhibition of phosphatidylinositol 3-kinase (PI3K) enzyme and human skin carcinoma cell growth by Combretum apiculatum Sond.

Abstract

The aim of this study was to determine the antiproliferative effect of an ethanolic leaf extract of Combretum apiculatum (CA) against human epidermoid carcinoma (A431) and human malignant melanoma (UCT-MEL1) cells, the toxic potential of CA on non-cancerous human keratinocytes (HaCat) and to evaluate the inhibitory activity against the phosphatidylinositol-3-kinase (PI3K) enzyme, which is involved in tumor survival and proliferation. The protective effect of CA on hepatocellular carcinoma (HepG2) cells, in which toxicity was induced using acetaminophen, was further determined. The CA extract was found to exhibit a 50% inhibitory concentration (IC50) of 56.40 ± 6.11 and 90.53 ± 4.94 µg/mL on A431 and UCT-MEL-1 cells respectively. Against non-cancerous HaCat cells an IC50 value of 62.20 ± 3.52 µg/mL was obtained, resulting in a selectivity index of 1.10 and 0.69 on A431 and UCT-MEL-1 cells respectively. Therefore, CA showed a higher selective antiproliferative effect towards squamous cell carcinoma cells. Combretum apiculatum was also found to have a protective effect against acetaminophen induced toxicity in HepG2 cells, with an 11% protection at 5 µg/mL. Lastly, the results from the PI3K assay revealed that CA was able to significantly inhibit the PI3K enzyme at each of the tested concentrations, with the highest inhibition noted at a concentration of 0.4 µg/mL with a relative percentage of 106.38 ± 26.36 %, which was comparable to the positive control, wortmannin. This study provides the first report of the activity of Combretum apiculatum against skin cancer cell lines and the potential inhibitory activity of this species on the PI3K enzyme.