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.
Highlights
As the primary cause of death, cancer is responsible for approximate 10 million deaths per year worldwide; the morbidity is increasing in both developing and developed countries [1]
We aim to explore a possible anti-cancer effect of the H. leucospilota protein by investigating the effects of H. leucospilota protein on cancer cell survival, migration, cell cycle, and apoptosis
We found that the H. leucospilota protein exerted its cytotoxic action through the induction of apoptosis, leading to the morphological changes in HepG2, A549, and Panc02 cancer cell lines
Summary
As the primary cause of death, cancer is responsible for approximate 10 million deaths per year worldwide; the morbidity is increasing in both developing and developed countries [1]. According to the World Health Organization (WHO), lung cancer (1.8 million deaths), colon and rectal cancer (935,000 deaths), liver cancer (830,000 deaths), stomach cancer (769,000 deaths) and breast cancer (685,000 deaths) are the top five cancers that cause the most deaths per year [2]. There is a pressing need to develop novel anti-cancer drugs that are broadspectrum, high potency, low toxicity and more cost effective. Marine creatures are an enriched ore of drug development; at least 10% of the marine organism extracts possess anti-tumor properties [7,8]. Marine organism extracts are characterized by high efficiency, safety, lower toxicity and reduced drug resistance [9]. The funders had no role in the study design, the data collection and analysis, the decision to publish, or the preparation of the manuscript
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