Proteomic Investigation to Identify Anticancer Targets of Nemopilema nomurai Jellyfish Venom in Human Hepatocarcinoma HepG2 Cells

Abstract

Nemopilema nomurai is a giant jellyfish that blooms in East Asian seas. Recently, N. nomurai venom (NnV) was characterized from a toxicological and pharmacological point of view. A mild dose of NnV inhibits the growth of various kinds of cancer cells, mainly hepatic cancer cells. The present study aims to identify the potential therapeutic targets and mechanism of NnV in the growth inhibition of cancer cells. Human hepatocellular carcinoma (HepG2) cells were treated with NnV, and its proteome was analyzed using two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI/TOF/MS). The quantity of twenty four proteins in NnV-treated HepG2 cells varied compared to non-treated control cells. Among them, the amounts of fourteen proteins decreased and ten proteins showed elevated levels. We also found that the amounts of several cancer biomarkers and oncoproteins, which usually increase in various types of cancer cells, decreased after NnV treatment. The representative proteins included proliferating cell nuclear antigen (PCNA), glucose-regulated protein 78 (GRP78), glucose-6-phosphate dehydrogenase (G6PD), elongation factor 1γ (EF1γ), nucleolar and spindle-associated protein (NuSAP), and activator of 90 kDa heat shock protein ATPase homolog 1 (AHSA1). Western blotting also confirmed altered levels of PCNA, GRP78, and G6PD in NnV-treated HepG2 cells. In summary, the proteomic approach explains the mode of action of NnV as an anticancer agent. Further characterization of NnV may help to unveil novel therapeutic agents in cancer treatment.

Nomad Jellyfish Rhopilema nomadica Venom Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Hepatocellular Carcinoma HepG2 Cells

“…Similar inhibitory effects against HepG2 cells have been reported for other jellyfish species such as Nemopilema nomurai , Cyanea lamarckii, and Acromitus flagellates venoms [ 35 , 37 , 38 , 39 , 40 ]. Interestingly, both Acromitus flagellates venom and Cyanea lamarckii extract share three to six protein bands with R. nomadica venom in their electrophoretic patterns [ 35 , 39 ].…”

Non-translational Connections of eEF1B in the Cytoplasm and Nucleus of Cancer Cells

“…The level of eEF1Bγ was increased in oral squamous cell carcinoma (Flores et al, 2016) and hepatic metastatic colorectal cancer (Yang et al, 2019). eEF1Bγ was downregulated in HepG2 cells treated with Nomura's jellyfish venom used as an anticancer drug (Choudhary et al, 2018). Also, the protein was essentially decreased in cervical cancer specimens taken from patients after treatment with paclitaxel and cisplatin (Liu et al, 2011).…”

Close association between abnormal expressed enzymes of energy metabolism and diarrhea-predominant irritable bowel syndrome

“…After separation in SDS-PAGE, the proteins on the gel were fixed and visualized by silver staining using a Silver Stain Plus Kit (Bio-Rad Laboratories Inc., Hercules) as described previously. [17] Scanning was carried out with an ImageScanner (Amersham Pharmacia Biotech) and image analysis was performed using ImageMaster 2D Platinum software, version 5.0. Proteins separated by 2-DE gels were quantitated in terms of their relative volume (% vol).…”