Background:

The sea cucumber potentials for stem cell proliferation induction and their mechanisms of bioactive compounds in its extract have been studied. Human umbilical cord mesenchymal stromal/stem cells (hUC-MSCs) were exposed to aqueous extract of Holothuria parva body wall.

Methods:

Using GC-MS analysis on aqueous extract of H. parva , proliferative molecules were detected. The extract concentrations of 5, 10, 20, 40, and 80 µg/mL and 10 and 20 ng/mL of human epidermal growth factor (EGF) as positive controls were used. MTT proliferation, cell count, viability, and cell cycle assays were performed. Using Western blot analysis, effects of aqueous extract of H. parva and EGF on cell proliferation markers were detected. Computational modeling done to detect effective proliferative compounds in aqueous extract of H. parva .

Results:

MTT assay showed that the 10, 20, and 40 µg/mL aqueous extract of H. parva had proliferative effects on hUC-MSCs. Count of the cells treated with the 20 µg/mL of the extract was increased faster and higher than the control group (P<0.05). This concentration of extract did not have significant effects on hUC-MSCs viability. The cell cycle assay of hUC-MSCs showed that percent of cells in the G2 stage of the extract was biologically higher than the control group (P>0.05). Expression of the cyclin D1, cyclin D3, cyclin E, HIF-1α, and TERT were increased comparing with the control group. Moreover, expression of the p21 and PCNA decreased after treating hUC-MSCs with the extract. However, the CDC-2/cdk-1 and ERK1/2 had almost the same expression as the control group. The expression of the cdk-4 and cdk-6 was decreased after treatment with the extract. Between the detected compounds, 1-methyl-4-(1-methylethenyl)-benzene showed better affinity to cdk-4 and p21 than tetradecanoic acid.

Conclusions:

The H. parva aqueous extract showed proliferative potential on the hUC-MSCs.