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Front. Pharmacol. | doi: 10.3389/fphar.2018.00127

Tricaproin isolated from Simarouba glauca inhibits the growth of human colorectal carcinoma cell lines by targeting class-1 histone deacetylases

  • 1Pharmacology, JSS College of Pharmacy, India
  • 2Department of Pharmacognosy and Phytopharmacy, JSS College of Pharmacy, India
  • 3pharmacology, JSS college of pharmacy, India
  • 4Biochemistry, Jagadguru Sri Shivarathreeswara University, India

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, dichloromethane, chloroform and 70% ethanol, 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.

Keywords: Simarouba glauca, Laxmitaru, Anti-cancer activity, Tricaproin, sodium butyrate, Histone Deacetylases, Apoptosis

Received: 14 Nov 2017; Accepted: 06 Feb 2018.

Edited by:

Akio Inui, Kagoshima University Graduate School of Medical and Dental Sciences, Japan

Reviewed by:

Parimal C. Sen, Bose Institute, India
Yi Yang, Guangzhou University of Chinese Medicine, China  

Copyright: © 2018 Jose, Chaitanya, Kannan and Madhunapantula. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Elango Kannan, JSS college of pharmacy, pharmacology, Head, Department of Pharmacology, JSS College of Pharmacy, Udhagamandalam, Tamil Nadu, India, Udhagamandalam, 643001, Tamil Nadu, India,
Dr. Subbarao V. Madhunapantula, Jagadguru Sri Shivarathreeswara University, Biochemistry, Center of Excellence in Molecular Biology and Regenerative Medicine, JSS Medical College, JSS University, Mysore, Karnataka, India, Mysore, 570015, Karnataka, India,