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.
Highlights
Primary liver cancer is the second leading cause of cancer-related death worldwide [1]
high performance liquid chromatography (HPLC) analysis of xanthone crude extract (XCE) was carried out using a C18 analytical column (3.9 × 150 mm) and approximately
A sample injection volume was adjusted to 10 μL and introduced into the HPLC system at a flow rate of 1.0 mL/min for 1 h with pure α-mangostin (α-MG) used as the standard
Summary
Primary liver cancer is the second leading cause of cancer-related death worldwide [1]. Doxorubicin, 5-fluorouracil (5-FU), and cisplatin are some of the commercial drugs used with systemic chemotherapy for liver cancer [4,5,6] They can cause numerous side effects as normal healthy cells that are actively dividing, such as those in bone marrow, the intestinal lining, and hair follicles, are affected. Another problem with chemotherapy for liver cancer is hypoxia-induced chemoresistance [7]. Reported pharmacologic properties of xanthone crude extract (XCE) include anti-cancer [11], antibacteria [12], and antidiabetic [13] effects. Hepatocellular carcinoma cell lines from zebrafish have been found to express similar genes to the human cell line, indicating their potential as a suitable animal model [27]
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