Anticancer potential of four triterpenoids against NCI-60 human tumor cell lines

Background

The burden of cancer incidences and mortality is rapidly increasing worldwide resulting in an increased demand for new therapies. Secondary metabolites extracted from medicinal plants have significantly contributed toward discovery of new cancer therapies some of which are in clinical use. In this study, anticancer potential of four triterpenoids, namely oleanonic acid (EK-2), 3-epi-oleanolic acid (EK-8), 1,2,3,22,23-pentahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene (EK-4) and 2,3,22,23-tetrahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene (EK-9), extracted from Ekebergia capensis Sparrm root bark was evaluated.

Results

We employed CLC-Pred to initially evaluate cytotoxicity of previously isolated compounds in silico where predictions revealed high probability of bioactivity. The compounds were then submitted to the National Cancer Institute (NCI), Developmental Therapeutics Program, for bioactivity evaluation against NCI-60 human tumor cell lines. The four compounds demonstrated a range of potencies at a concentration of 10 µM. The results revealed that EK-9 was the most potent with mean growth percent of 32.84 and cases of lethality (negative growth percent) against two leukemia cell lines (HL-60 (TB) and RPMI-8226) and HT29 (colon cancer) and SK-MEL-5 (melanoma). This molecule was further evaluated in a five-dose assay where notable growth inhibition against leukemia cells, HL-60 (TB), RPMI-8226 and K-562 was observed with growth inhibitory activity (GI₅₀) values of 3.10, 3.74 and 5.07 µM, respectively. In addition, total growth inhibition was observed at 11.2 μM and 18.9 μM for HL-60 (TB) and RPMI-8226 cells, respectively, partly accounting for the negative growth percent.

Conclusion

The study has demonstrated anticancer properties of the four triterpenoids with compound EK-9 being the most potent overall having selective bioactivity in leukemia and breast cancer cells. Further studies focusing on elucidating its mechanism of action will be useful in exploration of the therapeutic potential of triterpenoids in general.