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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.
Highlights
Annual reports on public safety are raising concerns about jellyfish envenomation
Venomous jellyfish species are found in both cubozoans, such as Chironex fleckeri, and scyphozoans (Cyanea capillata, Pelagia noctiluca, and Nemopilema nomurai) [3,4,5,6]
We have focused on Nemopilema nomurai in this study; it is one of the largest jellyfish species and can grow up to 2 m in bell diameter and 200 kg in weight [7]
Summary
Annual reports on public safety are raising concerns about jellyfish envenomation. Jellyfish stings are leading to a deleterious public health threat worldwide. It was previously reported that scorpion venom can inhibit the proliferation of cancer cells and primary tumors in animal models and can serve as a potential anticancer therapeutic [13,14]. A cardiotonic steroid (bufalin) extracted from toad venom (Bufo gargarizans cantor) exerts antitumor activity against numerous human cancer cell lines by inducing apoptosis and cell cycle arrest [22]. These characteristics of scorpion, snake, spider, and sea anemone venoms make them as a valuable source of therapeutic agents in cancer research.
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