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

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Faculty Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia
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Tasik Chini Research Centre, Faculty Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia
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Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia
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Faculty of Agro Based Industry, Universiti Malaysia Kelantan, Jeli Campus, Locked Bag 100, Jeli 17600, Kelantan, Malaysia
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ZACH Biotech Depot Private Limited, Cheras 43300, Selangor, Malaysia
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Danish Cancer Society Research Centre, Strandboulevarden 49, 2100 Copenhagen, Denmark
*
Author to whom correspondence should be addressed.
Toxics 2018, 6(4), 60; https://doi.org/10.3390/toxics6040060
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)
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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MDPI and ACS Style

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. https://doi.org/10.3390/toxics6040060

AMA Style

Fazry S, Noordin MAM, Sanusi S, Noor MM, Aizat WM, Lazim AM, Dyari HRE, Jamar NH, Remali J, Othman BA, Law D, Sidik NM, Cheah YH, Lim YC. Cytotoxicity and Toxicity Evaluation of Xanthone Crude Extract on Hypoxic Human Hepatocellular Carcinoma and Zebrafish (Danio rerio) Embryos. Toxics. 2018; 6(4):60. https://doi.org/10.3390/toxics6040060

Chicago/Turabian Style

Fazry, Shazrul, Muhammad A.M. Noordin, Salahuddin Sanusi, Mahanem M. Noor, Wan M. Aizat, Azwan M. Lazim, Herryawan R.E. Dyari, Nur H. Jamar, Juwairiah Remali, Babul A. Othman, Douglas Law, Nik M. Sidik, Yew H. Cheah, and Yi C. Lim 2018. "Cytotoxicity and Toxicity Evaluation of Xanthone Crude Extract on Hypoxic Human Hepatocellular Carcinoma and Zebrafish (Danio rerio) Embryos" Toxics 6, no. 4: 60. https://doi.org/10.3390/toxics6040060

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