Cytotoxicity and toxicity evaluation of xanthone crude extract on hypoxic human hepatocellular carcinoma and zebrafish (Danio rerio) 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.

Original languageEnglish
Article number60
JournalToxics
Volume6
Issue number4
DOIs
Publication statusPublished - 9 Oct 2018

Fingerprint

Cell proliferation
High performance liquid chromatography
Zebrafish
Cytotoxicity
Complex Mixtures
Organic compounds
Acetone
Hep G2 Cells
Toxicity
Hepatocellular Carcinoma
Embryonic Structures
Cells
Fluorouracil
Costs
Water
Inhibitory Concentration 50
Garcinia mangostana
xanthone
Drug and Narcotic Control
Tail

Keywords

  • Fish embryo toxicity test
  • HPLC
  • MTT proliferation assay
  • Xanthone
  • α-mangostin

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Chemical Health and Safety

Cite this

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title = "Cytotoxicity and toxicity evaluation of xanthone crude extract on hypoxic human hepatocellular carcinoma and zebrafish (Danio rerio) embryos",
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.",
keywords = "Fish embryo toxicity test, HPLC, MTT proliferation assay, Xanthone, α-mangostin",
author = "Sa`Ariwijaya, {Mohd Shazrul Fazry} and Noordin, {Muhammad Akram Mohd} and Salahuddin Sanusi and {Mat Noor}, Mahanem and {Wan Kamaruddin}, {Wan Mohd Aizat} and {Mat Lazim}, {Mohamad Azwani Shah} and {Eziwar Dyari}, {Herryawan Ryadi} and Jamar, {Nur Hidayah} and Juwairiah Remali and Othman, {Babul Airianah} and Douglas Law and Sidik, {Nik Marzuki} and Cheah, {Yew Hoong} and Lim, {Yi Chieh}",
year = "2018",
month = "10",
day = "9",
doi = "10.3390/toxics6040060",
language = "English",
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journal = "Toxics",
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T1 - Cytotoxicity and toxicity evaluation of xanthone crude extract on hypoxic human hepatocellular carcinoma and zebrafish (Danio rerio) embryos

AU - Sa`Ariwijaya, Mohd Shazrul Fazry

AU - Noordin, Muhammad Akram Mohd

AU - Sanusi, Salahuddin

AU - Mat Noor, Mahanem

AU - Wan Kamaruddin, Wan Mohd Aizat

AU - Mat Lazim, Mohamad Azwani Shah

AU - Eziwar Dyari, Herryawan Ryadi

AU - Jamar, Nur Hidayah

AU - Remali, Juwairiah

AU - Othman, Babul Airianah

AU - Law, Douglas

AU - Sidik, Nik Marzuki

AU - Cheah, Yew Hoong

AU - Lim, Yi Chieh

PY - 2018/10/9

Y1 - 2018/10/9

N2 - 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.

AB - 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.

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KW - α-mangostin

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