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Toxics 2018, 6(4), 60; https://doi.org/10.3390/toxics6040060

Cytotoxicity and Toxicity Evaluation of Xanthone Crude Extract on Hypoxic Human Hepatocellular Carcinoma and Zebrafish (Danio rerio) Embryos

1
Faculty Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia
2
Tasik Chini Research Centre, Faculty Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia
3
Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia
4
Faculty of Agro Based Industry, Universiti Malaysia Kelantan, Jeli Campus, Locked Bag 100, Jeli 17600, Kelantan, Malaysia
5
ZACH Biotech Depot Private Limited, Cheras 43300, Selangor, Malaysia
6
Danish Cancer Society Research Centre, Strandboulevarden 49, 2100 Copenhagen, Denmark
*
Author to whom correspondence should be addressed.
Received: 9 September 2018 / Revised: 26 September 2018 / Accepted: 4 October 2018 / Published: 9 October 2018
(This article belongs to the Special Issue Contaminant Effects on Zebrafish Embryos)
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Abstract

Xanthone is an organic compound mostly found in mangosteen pericarp and widely known for its anti-proliferating effect on cancer cells. In this study, we evaluated the effects of xanthone crude extract (XCE) and α-mangostin (α-MG) on normoxic and hypoxic human hepatocellular carcinoma (HepG2) cells and their toxicity towards zebrafish embryos. XCE was isolated using a mixture of acetone and water (80:20) and verified via high performance liquid chromatography (HPLC). Both XCE and α-MG showed higher anti-proliferation effects on normoxic HepG2 cells compared to the control drug, 5-fluorouracil (IC50 = 50.23 ± 1.38, 8.39 ± 0.14, and 143.75 ± 15.31 μg/mL, respectively). In hypoxic conditions, HepG2 cells were two times less sensitive towards XCE compared to normoxic HepG2 cells (IC50 = 109.38 ± 1.80 μg/mL) and three times less sensitive when treated with >500 μg/mL 5-fluorouracil (5-FU). A similar trend was seen with the α-MG treatment on hypoxic HepG2 cells (IC50 = 10.11 ± 0.05 μg/mL) compared to normoxic HepG2 cells. However, at a concentration of 12.5 μg/mL, the α-MG treatment caused tail-bend deformities in surviving zebrafish embryos, while no malformation was observed when embryos were exposed to XCE and 5-FU treatments. Our study suggests that both XCE and α-MG are capable of inhibiting HepG2 cell proliferation during normoxic and hypoxic conditions, more effectively than 5-FU. However, XCE is the preferred option as no malformation was observed in surviving zebrafish embryos and it is more cost efficient than α-MG. View Full-Text
Keywords: xanthone; α-mangostin; HPLC; MTT proliferation assay; fish embryo toxicity test xanthone; α-mangostin; HPLC; MTT proliferation assay; fish embryo toxicity test
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Fazry, S.; Noordin, M.A.M.; Sanusi, S.; Noor, M.M.; Aizat, W.M.; Lazim, A.M.; Dyari, H.R.E.; Jamar, N.H.; Remali, J.; Othman, B.A.; Law, D.; Sidik, N.M.; Cheah, Y.H.; Lim, Y.C. Cytotoxicity and Toxicity Evaluation of Xanthone Crude Extract on Hypoxic Human Hepatocellular Carcinoma and Zebrafish (Danio rerio) Embryos. Toxics 2018, 6, 60.

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