While anticancer properties of Simarouba glauca (SG, commonly known as Paradise tree) are well documented in ancient literature, the underlying mechanisms leading to cancer cell death begin to emerge very recently. The leaves of SG have been used as potential source of anticancer agents in traditional medicine. Recently attempts have been made to isolate anticancer agents from the leaves of SG using solvent extraction, which identified quassinoids as the molecules with tumoricidal activity. However, it is not known whether the anti-cancer potential of SG leaves is just because of quassinoids alone or any other phytochemicals also contribute for the potency of SG leaf extracts. Therefore, SG leaves were first extracted with hexane, chloroform, ethyl acetate, 70% ethanol, water and anti-cancer potential (for inhibiting colorectal cancer (CRC) cells HCT-116 and HCT-15 proliferation) determined using Sulforhodamine-B (SRB) assay. The chloroform fraction with maximal anticancer activity was further fractionated by activity-guided isolation procedure and structure of the most potent compound determined using spectral analysis. Analysis of the structural characterization data showed the presence of tricaproin (TCN). TCN inhibited CRC cells growth in a time- and dose dependent manner but not the normal cell line BEAS-2B. Mechanistically, TCN reduced oncogenic Class-I Histone deacetylases (HDACs) activity, followed by inducing apoptosis in cells. In conclusion, the anti-cancer potential of SG is in part due to the presence of TCN in the leaves.

Simarouba glauca DC (Family: Simaroubaceae, abbreviated as S. glauca / SG), commonly known as 'Laxmitaru' or 'Paradise tree' is an eco-friendly tree that grows in tropical areas of America, The West Indies and Brazil. Nutritionally, SG has been used as a potential source of edible oil. Medicinally, the decoction prepared from SG leaves has been demonstrated to exhibit antitumor, antimalarial, antiviral activities. Objectives: Address various existing gaps in the research on Simarouba glauca and provide future directions to promote address these grey areas. Methods: Literature pertaining to Simarouba glauca and various related plants was collected using PubMed search engine with key words Simarouba glauca, Simaroubaceae, Paradise tree, Laxmitaru. Articles pertaining to anti-cancer activity were filtered and information collected for preparing the review article. Although pharmacological potential of Simarouba glauca is well documented; not much is known about the mechanism(s) of action of the isolated phytoconstituents. In addition, many gaps pertaining to the efficacy of pharmacological agents for inhibiting cancers does exist. Therefore, future studies should focus on (a) screening and isolating key pharmacological agents that exhibit better safety and efficacy profiles for treating cancers; (b) evaluating the pharmacodynamic and pharmacokinetic properties of phytochemicals in experimental animal models; (c) testing the compounds in clinical trials; and (d) developing better strategies to effectively deliver the isolated compounds from SG. Studies are also warranted to determine whether isolated compounds of SG are better or the crude extracts that contain a combination of agents are better. Extensive research is required to address various unanswered questions. Therefore, future studies should focus on providing answers to fill the existing gaps about the utility of Simarouba glauca phytochemicals for treating cancers.

Emerging advancements in anticancer drug discovery research are leaning towards the plant-based bioactive fractions, which is a cocktail of naturally abundant two or more substances with unique proportions, exhibiting greater potential to combat cancers than the individual molecules. Thus, isolation and characterization of anticancer activity enriched fractions from plants is gaining scientific attention. Consistent with this view, one of the evidence-based traditional medicinal plants, well known for its anti-cancer potential, Simarouba glauca (SG) leaf has been scientifically examined to identify and isolate the potent anti-cancer fraction. The dried SG leaves were extracted successively with the solvents of increasing polarity. The phytochemical characterization of obtained extracts and fractions were carried out to determine the phenolic acid composition. All fractions were individually examined for anti-cancer property in cancer cells representing lungs, cervix, breast, colon and rectum in vitro. Among all fractions tested, the chloroform (SGC) and ethyl acetate (SGEA) extracts showed potent antiproliferative effects by triggering apoptosis. In summary, our findings demonstrate that the extracts SGC and SGEA have potent anti-cancer activities compared to other fractions of SG leaf and thus warrant further preclinical studies to establish scientific basis for the anticancer potentials of SG.

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