Antitumor Activity of Simarouba tulae Extracts in a Panel of Cancer Cell Lines

Abstract

Cancer is among the principal causes of death globally. Statistics from the American Cancer Society project an increase of 50% in new cases and 60% in worldwide deaths by 2030. Although several chemotherapeutic agents are currently being used for the treatment of most cancer types, recurrence, drug resistance, and severe side effects demand the need for alternative novel drugs. Even with the evolution of synthetic chemistry, nature remains as a fundamental source of molecular diversity and structural innovation. Of the 140 anti‐cancer agents approved since 1940, over 60% could be traced to a natural product. One of the most popular bioactive molecules found in natural extracts are quassinoids which are highly oxygenated triterpenes found in the Simaroubaceae family. Simalikalactone D is a quassinoid isolated from Simarouba tulae, an endemic tree from Puerto Rico. Our objective was to evaluate the anticancer effect of this Simalikalactone D in a panel of human cancer cell lines. The cytotoxicity was evaluated in vitro through dose‐response assays in A2780CP20 cisplatin‐resistant ovarian cancer and in MDA‐MB‐231 breast cancer cell lines. Our results showed that Simalikalactone D exhibits significant cytotoxicity against both cell lines. Partial organic extracts of Simarouba also were toxic to these cells lines. The IC50 values were around 50–100 nM which indicate that Simalikalactone D is a potential anticancer drug. Ongoing experiments evaluate the cytotoxicity of Simalikalactone D in other cancer cell types including colon and prostate cancer cells, and in normal cells. To assess the mechanism of action of this compound, future experiments will measure the effect of Simalikalactone D on activation of apoptosis, cell cycle progression arrest and in proteins associated – with these biological effects.Support or Funding InformationResearch reported in this publication was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103475.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.