RC-6 ribonuclease induces caspase activation, cellular senescence and neuron-like morphology in NT2 embryonal carcinoma cells

Abstract

Abstract.Frog ribonucleases have been demonstrated to have anticancer activities. However, whether RC-6 ribonuclease exerts anticancer activity on human embryonal carcinoma cells remains unclear. In the present study, RC-6 induced cytotoxicity in NT2 cells (a human embryonal carcinoma cell line) and our studies showed that RC-6 can exert anticancer effects and induce caspase-9 and -3 activities. Moreover, to date, there is no evidence that frog ribonuclease-induced cytotoxicity effects are related to cellular senescence. Therefore, our studies showed that RC-6 can increase p16 and p21 protein levels and induce cellular senescence in NT2 cells. Notably, similar to retinoic acid-differentiated NT2 cells, neuron-like morphology was found on some remaining live cells after RC-6 treatment. In conclusion, our study is the first to demonstrate that RC-6 can induce cytotoxic effects, caspase-9/-3 activities, cellular senescence and neuron-like morphology in NT2 cells.

In Vitro Anticancer Effect of Gedunin on Human Teratocarcinomal (NTERA-2) Cancer Stem-Like Cells

“…Gedunin exerted a potential antiproliferative effect on cancer stem cell model NTERA-2 cells when compared to the positive control retinoic acid. Several researchers have also shown antiproliferative effects of certain compounds such as rooperol and RC-6 ribonuclease in NTERA-2 cells in vitro [17, 23]. …”

Amphibian-Derived Natural Anticancer Peptides and Proteins: Mechanism of Action, Application Strategies, and Prospects

“…Additionally, certain ribonucleases derived from amphibians [ 63 ], such as RC-6 from bullfrogs, have demonstrated anticancer properties. For example, RC-6 has been shown to elevate the levels of the p16 protein in human embryonic carcinoma cells (NT2) and induce cell senescence [ 64 ].…”

“…These findings suggest that Dermaseptin-PS1 can induce endogenous apoptotic pathways, exhibiting anti-glucose Glioma activity [ 54 ]. Several other proteins, including Ranatuerin-2PLx from the pickerel frog [ 39 ], ribonuclease RC-6 from Rana catesbeiana [ 64 ], and protein toxin BMP1 from the Indian toad ( Bufo melanostictus , Schneider ) [ 9 , 59 ], are also capable of inducing endogenous apoptosis.…”