Abstract
Jellyfish venom is a rich source of bioactive proteins and peptides with various biological activities including antioxidant, antimicrobial and antitumor effects. However, the anti-proliferative activity of the crude extract of Rhopilema nomadica jellyfish venom has not been examined yet. The present study aimed at the investigation of the in vitro effect of R. nomadica venom on liver cancer cells (HepG2), breast cancer cells (MDA-MB231), human normal fibroblast (HFB4), and human normal lung cells (WI-38) proliferation by using MTT assay. The apoptotic cell death in HepG2 cells was investigated using Annexin V-FITC/PI double staining-based flow cytometry analysis, western blot analysis, and DNA fragmentation assays. R. nomadica venom displayed significant dose-dependent cytotoxicity on HepG2 cells after 48 h of treatment with IC50 value of 50 μg/mL and higher toxicity (3:5-fold change) against MDA-MB231, HFB4, and WI-38 cells. R. nomadica venom showed a prominent increase of apoptosis as revealed by cell cycle arrest at G2/M phase, upregulation of p53, BAX, and caspase-3 proteins, and the down-regulation of anti-apoptotic Bcl-2 protein and DNA fragmentation. These findings suggest that R. nomadica venom induces apoptosis in hepatocellular carcinoma cells. To the best of the authors’ knowledge, this is the first scientific evidence demonstrating the induction of apoptosis and cell cycle arrest of R. nomadica jellyfish venom.
Highlights
Accepted: 17 August 2021Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related mortality globally [1]
The present study showed that crude venom of R. nomadica jeljellyfish inhibited the growth of HepG2 cells in a dose-dependent manner
We demonstrate the intrinsic apoptotic pathway induced by R. nomadica venom in HepG2 cells through the elevation of BAX/Bcl-2 ratio leading to triggering of caspase-3 signaling protein, which causes cells destruction and ends up to apoptosis
Summary
Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related mortality globally [1]. The use of these routine treatments is assigned with potent toxic adverse effects in addition to the development of resistance of HCC cells to anticancer drugs [6,7]. In this perspective, there is an unmet need for novel anticancer agents that may have different mechanisms of action from current therapies, leading to higher selectivity for HCC cells. Jellyfish venom is primarily confined in specialized venom-containing capsules known as nematocysts that are found mainly in the tentacles
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