Cancer Cell Inhibiting Sea Cucumber (Holothuria leucospilota) Protein as a Novel Anti-Cancer Drug

Abstract

Cancer remains the primary cause of death worldwide. To develop less toxic anti-cancer drugs to relieve the suffering and improve the survival of cancer patients is the major focus in the anti-cancer field. To this end, marine creatures are being extensively studied for their anti-cancer effects, since extracts from at least 10% of the marine organisms have been shown to possess anti-tumor activities. As a classic Chinese traditional medicine, sea cucumbers and compounds extracted from the sea cucumbers, such as polysaccharides and saponins, have recently been shown to exhibit anti-cancer, anti-inflammatory, and anti-oxidant effects. Holothuria leucospilota (H. leucospilota) is a tropical edible sea cucumber species that has been successfully cultivated and farmed in large scales, providing a readily available source of raw materials to support the development of novel marine anti-cancer drugs. However, very few studies have so far been performed on the biological activities of H. leucospilota. In this study, we first investigated the anti-cancer effect of H. leucospilota protein on three cancer cell lines (i.e., HepG2, A549, Panc02) and three normal cell lines (NIH-3T3, HaCaT, 16HBE). Our data showed that H. leucospilota protein decreased the cell viabilities of HepG2, A549, HaCaT, 16HBE in a concentration-dependent manner, while Panc02 and NIH-3T3 in a time- and concentration-dependent manner. We also found that the inhibitory effect of H. leucospilota protein (≥10 μg/mL) on cell viability is near or even superior to EPI, a clinical chemotherapeutic agent. In addition, our data also demonstrated that H. leucospilota protein significantly affected the cell cycle and induced apoptosis in the three cancer cell lines investigated; in comparison, it showed no effects on the normal cell lines (i.e., NIH-3T3, HaCaT and 16HBE). Finally, our results also showed that H. leucospilota protein exhibited the excellent performance in inhibiting cell immigrations. In conclusion, H. leucospilota protein targeted the cancer cell cycles and induced cancer cell apoptosis; its superiority to inhibit cancer cell migration compared with EPI, shows the potential as a promising anti-cancer drug.

Anticancer and anticholesterol attributes of sea cucumbers: An opinion in terms of functional food applications

“…Marine organisms are augmented for development of drugs; about 10% of these creatures' extracts contain anticancer attributes. In addition, the organisms' extracts are categorized by reduced drug resistance, lower toxicity, safety, and high efficiency ( 5 ). Sea cucumber has been explored for its anticancer and cholesterol-lowering activities due to the presence of potential bioactive components ( Figure 1 ).…”

“…Some commonly consumed sea cucumbers that possess health benefits are Holothuria leucospilota, Bohadschia argus, Pearsonothuria graeffei, Holothuria polii, Colochirusancep, Holothuria arenicola, Cucumaria japonica , and several others ( 4 ). Sea cucumbers contain numerous bioactive compounds such as chondroitin sulfates, saponins, peptides, and glycosaminoglycan, and these compounds possess anticoagulation, antiangiogenesis, anticancer, antidiabetic, and antibacterial activities ( 5 ). Besides, sea cucumbers also contain micronutrients such as thiamine or vitamin B1, B2 or riboflavin, B3 (niacin), vitamin A (retinol, retinyl esters), calcium, iron, zinc, and magnesium ( 4 ).…”

“…Both properties are shown to exert hypocholesterolemic effects ( 3 ). Sea cucumbers also contain certain proteins (bioactive peptides), polysaccharides, and saponins, and when extracted, these compounds are shown to exert anticancer effects ( 4 , 5 ). Saponins from sea cucumbers promote osteoblast differentiation or osteogenic differentiation from pre-osteoblasts by activating molecular pathways of BMP2/Smads activation in MC3T3-E1 cells ( 6 ).…”

Marine Migrastatics: A Comprehensive 2022 Update

“…Not only single peptides or proteins but also crude protein extracts have demonstrated potent migrastatic bioactivity. This is the case of proteins extracted from sea cucumber ( Holothuria leucospilota ) that have shown a potential anti-cancer activity towards human hepatoma HepG2 cells, human lung carcinoma A549 cells, and human pancreatic cancer Panc02 cells, with a higher efficacy than a clinical anti-cancer drug [ 80 ].…”

Identification and Pharmacological Activities of Secondary Metabolites of Phytochemicals

“…osteoporosis [44][45][46], cancers [47][48][49][50][51], chronic obstructive pulmonary diseases [52][53][54], diabetes [41,[55][56][57], diarrheal [58], respiratory problems [59], Human Immunodeficiency Virus (HIV) infection [13,[60][61][62], mental health problems [24,[63][64][65][66][67] etc.…”