Antimetastatic activity of seongsanamide B in γ-irradiated human lung cancer

Abstract

Lung cancer, which has a high incidence and mortality rates, often metastasizes and exhibits resistance to radiation therapy. Seongsanamide B has conformational features that suggest it has therapeutic potential; however, its antitumor activity has not yet been reported. We evaluated the possibility of seongsanamide B as a radiation therapy efficiency enhancer to suppress γ-irradiation-induced metastasis in non-small cell lung cancer. Seongsanamide B suppressed non-small cell lung cancer cell migration and invasion caused by γ-irradiation. Furthermore, it suppressed γ-irradiation-induced upregulation of Bcl-XL and its downstream signaling molecules, such as superoxide dismutase 2 (SOD2) and phosphorylated Src, by blocking the nuclear translocation of phosphorylated STAT3. Additionally, seongsanamide B markedly modulated the γ-irradiation-induced upregulation of E-cadherin and vimentin. Consistent with the results obtained in vitro, while seongsanamide B did not affect xenograft tumor growth, it significantly suppressed γ-irradiation-induced metastasis by inhibiting Bcl-XL/SOD2/phosphorylated-Src expression and modulating E-cadherin and vimentin expression in a mouse model. Thus, seongsanamide B may demonstrate potential applicability as a radiation therapy efficiency enhancer for lung cancer treatment.

Keywords

• Lung cancer
• Metastasis
• Seongsanamide B
• Radiation therapy enhancer