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Molecules 2018, 23(11), 2733; https://doi.org/10.3390/molecules23112733

Cytotoxic Effects of Pinnatane A Extracted from Walsura pinnata (Meliaceae) on Human Liver Cancer Cells

1
Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia
2
Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia
3
Centre for Foundation Studies in Science, University of Malaya, Kuala Lumpur 50603, Malaysia
4
Centre for Research in Biotechnology for Agriculture (CEBAR), University of Malaya, Kuala Lumpur 50603, Malaysia
5
Centre of Natural Products and Drug Discovery (CENAR), University of Malaya, Kuala Lumpur 50603, Malaysia
*
Author to whom correspondence should be addressed.
Received: 24 August 2018 / Revised: 2 October 2018 / Accepted: 3 October 2018 / Published: 23 October 2018
(This article belongs to the Section Medicinal Chemistry)
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Abstract

Background: Pinnatane A from the bark of Walsura pinnata was investigated for its anti-cancer properties by analyzing the cytotoxic activities and cell cycle arrest mechanism induced in two different liver cancer cell lines. Methods: A 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to analyze the pinnatane A selectivity in inducing cell death in cancer and normal cells. Various biological assays were carried out to analyze the anti-cancer properties of pinnatane A, such as a live/dead assay for cell death microscopic visualization, cell cycle analysis using propidium iodide (PI) to identify the cell cycle arrest phase, annexin V-fluorescein isothiocyanate (annexin V-FITC)/PI flow cytometry assay to measure percentage of cell populations at different stages of apoptosis and necrosis, and DNA fragmentation assay to verify the late stage of apoptosis. Results: The MTT assay identified pinnatane A prominent dose- and time-dependent cytotoxicity effects in Hep3B and HepG2 cells, with minimal effect on normal cells. The live/dead assay showed significant cell death, while cell cycle analysis showed arrest at the G0/G1 phase in both cell lines. Annexin V-FITC/PI flow cytometry and DNA fragmentation assays identified apoptotic cell death in Hep3B and necrotic cell death in HepG2 cell lines. Conclusions: Pinnatane A has the potential for further development as a chemotherapeutic agent prominently against human liver cells. View Full-Text
Keywords: anti-cancer; apoptosis; cell cycle arrest; necrosis; triterpene anti-cancer; apoptosis; cell cycle arrest; necrosis; triterpene
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Zakaria, N.; Mahdzir, M.A.; Yusoff, M.; Mohd Arshad, N.; Awang, K.; Nagoor, N.H. Cytotoxic Effects of Pinnatane A Extracted from Walsura pinnata (Meliaceae) on Human Liver Cancer Cells. Molecules 2018, 23, 2733.

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