α-Mangosteen as An Oxidative Inhibitor in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the second leading cause of cancer mortality worldwide. Many strategies to discover molecular-based therapy are currently being implemented to overcome the resistance in HCC treatment. Cancer research is more targeted at molecular level of natural ingredients treatment as chemoprevention to reduce carcinogenesis risk. One of the natural compounds that serve as chemopreventive agent is mangosteen. α-Mangosteen, a xanthone commonly found in the fruit hull of Garcinia mangostana Linn, possess as an antioxidant. This study aims to determine the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and protein carbonyl (PC) as the biomarkers of oxidative stress on untreated HepG2 cells compared to α-mangosteen-treated HepG2 cells. The results indicated that α-mangosteen has a cytotoxic effect on HepG2 cells with IC50=242.58 μg/mL and reduced ROS level 23.15±4.29% at 200 μg/mL. The MDA level of HepG2 cells was not significantly higher than on WRL-68 by 7.6%, 17.93%, 28.8%, 35.32%, and 61.95% at 100, 200, 500, 800, and 1000 μg/mL respectively. α-Mangosteen at 100 and 200 μg/mL reduced protein carbonyl by 76.24 and 79.84% in HepG2 cells line while compared to normal liver cells line (WRL-68) significantly (P<0.05). In conclusion, α-mangosteen reduced levels of ROS, MDA and PC. Therefore, α-mangosteen is a potential anti-cancer agent through oxidative stress inhibition.Keyword: free radical, HepG2 cells, α-mangosteen, oxidative stress.

Different Modes of Mechanism of Gamma-Mangostin and Alpha-Mangostin to Inhibit Cell Migration of Triple-Negative Breast Cancer Cells Concerning CXCR4 Downregulation and ROS Generation

“…Moreover, α-mangostin-induced ROS overproduction might activate the PI3K/AKT signaling pathway, inhibiting cancer cell proliferation, migration, and induction of mitochondrial dysfunction that mediates apoptosis in MDA-MB-231 cells ( 23 ). Another finding also revealed that α-mangostin enhanced higher ROS accumulation in hepatoblastoma HepG2 cells than in hepatocyte WRL-68 cells, which could imply the selectivity of α-mangostin in cells ( 43 ).…”

The metabolic and molecular mechanisms of α‑mangostin in cardiometabolic disorders (Review)

“…However, when assessing MdA levels, α-mangostin led to a more significant MDA reduction in the HepG2 cancer line, possibly due to the increased oxidative stress in comparison with the WRL-68 cell line. Notably, when compared to WRL-68, a normal human hepatic cell line, HepG2 cell line presented with a more notable reduction of MdA (109). It is possible that HepG2 presented with more reduced MdA because of the effects of both ROS that stabilizes Nrf2, and oncogenic signaling via KRAS and BRAF that has been revealed to induce Nrf2 stabilization (110), leading to enhanced production of antioxidant proteins.…”

Evaluation of The Anticancer Activity of Hydroxyxanthones Against Human Liver Carcinoma Cell Line

“…It was reported that the interactions with key amino acid residues of EGFR, i.e., Glycine695, Glycine700, Glutamine767, Methionine769, Aspartic acid831, Glycine833, Arginine812, Asparagine818, and Tyrosine845 were pivotal to the suppression of cancer cell division [7] 2). It was reported that the interactions with Glutamic acid640, Cysteine673, and Aspartic acid810 residues were critical to deactivating the PDGFR function leading to the suppression of cancer cell proliferation [12]. From the molecular docking data, the 1,3,6,8tetrahydroxyxanthone interacted with all these key amino acid residues at the hinge region αC-helix DFG motif of the activation loop of PDGFR.…”

“…Meanwhile, the interactions of 1,3,6,8tetrahydroxyxanthone with Glutamine767 and Methionine769 through hydrogen bonds, as well as Aspartic acid831 through van der Waals interaction, on the active site of EGFR caused the less signal for the cancer cells to proliferate, differentiate and survive [7] [8]. On the other hand, the ability of 1,3,6,8-tetrahydroxyxanthone to interact with Cysteine673 and Aspartic acid810 through hydrogen bonds on the active site of PDGFR protein receptor, as well as with Glutamine640 through van der Waals, suppress the regulation of cancer cell to migrate, survive and proliferate [12].…”

“…These phenomena lead to the apoptosis and death of cancer cells [6]. EGFR protein receptor plays an important role in cancer cell signaling pathways that control cancer cell survival, differentiation, and proliferation [7]- [9], while PDGFR protein regulates the cancer cell migration, survival, and proliferation [10]- [12]. When these protein receptors are inhibited, the cancer cells can not be spread out and multiplied, thus leading to the death of cancer cells.…”