Abstract
Background and Objective: Hepatocellular carcinoma (HCC) is a public health problem and one of the common causes of mortality around the world. Zamzam water (ZW) contains metallocenes that were reported as promising anticancer agents by blocking DNA replication. The purpose of the current study was to explore the antiproliferative effect of ZW against HCC in vitro. Materials and Methods:To achieve this goal, elemental analysis by inductively coupled plasma mass spectrometry (ICP-MS) was used for metal testing in ZW and tap water (TW), as well as metal-free water sources, deionized water (DW) and double deionized water (DDW). Water was applied in vitro on hepatic cancer HepG2 cells to test their cytotoxic effects and the underlining apoptotic mechanism. One-way ANOVA was used as a statistical method to compare between treated and untreated groups. Results: It was found that ZW is explicitly rich in Na, Ca and Mg ions which are essential for biological homeostasis in human beings. Moreover, it was reported that ZW has an oncolytic property, owing to the presence of V, Fe and Se, where it produces the highest killing effect with about 35% of cell death associated with mitochondrial impairment with a dose dependent decrease in cell viability of HepG2 cells upon treatment. To test the underlining mechanism of the anti-cancer effect of ZW, apoptosis was performed to investigate the apoptotic signals. It was found that ZW killed the HepG2 cells through apoptosis. Mechanistically, 0.84% of the pro-apoptotic cells increased significantly to be 38% post-treatment with 50% ZW v/v. Conclusion: The balanced nutritional composition of ZW could be of great interest, synergizing with other anti-cancer components to thwart cancer progression.