Bioassay-Guided Isolation and Evaluation of Antiproliferative Effects of (Z)-Ethylidene-4, 6-Dimethoxycoumaran-3-One from Pogostemon Quadrifolius (Benth.)

Cheriyamundath, Sanith; Raghavan, Rahul; Banerji, Asoke; Klika, Karel D; Ulrich, Cornelia; Owen, Robert W; Madassery, Joseph

doi:10.22034/APJCP.2017.18.7.1783

Bioassay-Guided Isolation and Evaluation of Antiproliferative Effects of (Z)-Ethylidene-4, 6-Dimethoxycoumaran-3-One from Pogostemon Quadrifolius (Benth.)

Document Type : Research Articles

Authors

¹ Department of Biotechnology, University of Calicut, Malappuram, Kerala, India.

² Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kollam, Kerala, India.

³ Molecular Structure Analysis, German Cancer Research Center (DKFZ), Germany.

⁴ Division of Preventive Oncology, National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Germany.

10.22034/APJCP.2017.18.7.1783

Abstract

The aim of the study was to isolate and identify the major cytotoxic principle from plant leaves of Pogostemon quadrifolius (Benth.) and evaluate its antiproliferative potential against human cancer cells. Plant leaves were extracted sequentially with a soxhlet apparatus, using petroleum ether, chloroform and methanol solvents. Petroleum ether and chloroform extracts exhibited antiproliferative properties against Caco-2, HeLa, THP-1, MCF-7 and Jurkat E6-1cancer cell lines tested, but methanol extracts failed to exhibit such activity. The major antiproliferative principle from petroleum ether and chloroform extracts was isolated with the help of bioassay guided column chromatography. This cytotoxic compound was further analysed by UV, TLC, HPLC, LC-MS, GC-MS and NMR analyses and was identified to be novel: (Z)-ethylidene-4,6-dimethoxycoumaran-3-one (Compound 1). The half-maximal inhibitory concentrations for proliferation (IC50) exhibited by compound 1 were 19.4, 23.1, 22.1, 35.9 and 8.32 μM against Caco-2, HeLa, THP-1, MCF-7 and Jurkat E6-1 cancer cell lines, respectively. Further experiments revealed that compound 1 triggered the apoptosis mode of cell death in cancer cell lines. Thus, the present study allowed isolation and identification of a novel cytotoxic natural compound, (Z)-ethylidene-4,6-dimethoxycoumaran-3-one, from plant leaves of P. quadrifolius (Benth.). Our pre-clinical study also indicated that compound 1 is particularly active in the acute T cell leukemia cell line (Jurkat E6-1) with potential for application as a chemotherapeutic agent in the future.

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