UVB-irradiated indole-3-acetic acid induces apoptosis via caspase activation

Abstract

Objective: Indole-3-acetic acid (IAA) activation has been suggested as a new strategy for cancer therapy. It has been reported that ultraviolet B (UVB) radiation can activate IAA. In the present study, we investigated whether UVB-irradiated IAA (IAA(UVB)) can induce apoptosis of G361 human melanoma cells and examined the apoptotic pathway involved. Methods: DNA fragmentation was measured to examine apoptosis. IAA(UVB)-induced signaling pathways were investigated by Western blot analysis. Results: Our results show that IAA(UVB) reduced cell viability of G361 human melanoma cells, and induced DNA fragmentation, a hallmark of apoptosis. We also found that c-Jun NH 2-terminal kinase (JNK) and p38, which are activated by IAA(UVB), are not associated with this cell death. We further investigated the IAA(UVB)-mediated apoptotic pathway after pretreatment with NS398, vitamin C, and N-acetylcysteine (NAC). Although NS398, an inhibitor of cyclooxygenase-2, was not protective, vitamin C and NAC ameliorated IAA(UVB)-mediated cell death. In addition, when cells were pretreated with a caspase inhibitor, IAA(UVB)-induced apoptosis was inhibited. Conclusions: These results suggest that free radicals generated from IAA by UV irradiation may cause apoptosis, and IAA(UVB) induces apoptosis of G361 human melanoma cells by activating caspases.