A conotoxin-derived peptide exerts anti-tumor effects in ovarian cancer associated with activation of JNK/JunB signaling.

The discovery of potent anticancer peptides (ACPs) represents a crucial avenue in current targeted tumor therapy. This study systematically evaluated the broad-spectrum antitumor potential of sPep2, a peptide derived from Conus venom. In vitro investigations demonstrated that sPep2 exhibited potent cytotoxic activity against cancer cells from diverse tissue origins. Notably, its efficacy against ovarian cancer cells was comparable to that of melittin, with a more favorable in vitro selectivity profile. Beyond direct cytotoxicity, sPep2 at sublethal concentrations significantly inhibited tumor cell proliferation. Mechanistic studies indicated that sPep2-induced apoptosis was associated with activation of c-Jun N-terminal kinase (JNK) signaling, accompanied by the upregulation and accumulation of JunB-a member of the activator protein 1 (AP-1) transcription factor family-whereas c-Jun remained unchanged. Furthermore, in vivo ovarian cancer models showed that sPep2 exhibited favorable antitumor efficacy without overt treatment-related toxicity. In conclusion, this study not only identifies sPep2 as a promising hit molecule with broad-spectrum anticancer activity but also suggests that its effects are associated with activation of JNK/JunB signaling.