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Objectives   This work aimed to enhance anti-skin cancer activities of  Apostichopus japonicus , spiky sea cucumber, through ultrasonification extraction process at low temperature.Methods   Dried  Apostichopus japonicus  was extracted with an ultrasonification process at 50°C and 95 kHz for two hours (UE), and anti-skin cancer activities of the extract from the UE were also compared with those from conventional extraction processes using hot water (WE) or 70% ethanol at 80°C (EE) for 12 hours.Results   The amount of canthaxanthin in the UE was higher than that in the WE or EE, and its cytotoxicity against human keratinocytes was less than the others. The extract from the UE showed 93.5% inhibition against human malignant cell growth, which was also higher than those from both WE and EE. The extract from the UE demonstrated the ability of inhibiting both cancer cell proliferation and metastasis by downregulating the skin tumor-promoting genes such as Bcl-2, STAT3, and MMP-9.Conclusions   The ultrasonification process was proved to be effective especially in extracting heat-sensitive marine biomass,  A. japonicus  having higher amounts of canthaxanthin and better anti-skin cancer activities, possibly due to less destruction and high elution of bioactive substances under low temperature extraction condition.

Anti-Skin Cancer Activities of Apostichopus japonicus Extracts from Low-Temperature Ultrasonification Process