Gigantol-induced apoptosis in lung cancer cell through mitochondrial-dependent pathway

Abstract

Lung cancer is identified as a major cause of cancer-related death. Death in this cancer associates with the acquisition of apoptosis avoidance mechanism. Apoptosis, a programmed cell death mechanism, plays an important role on normal cell development and tissue homeostasis. The aberrances on cell death mechanism contribute to several pathogenesis including cancers. Several efforts have been paid in investigation of anticancer agents from natural sources. Gigantol (GG), an agent isolated from Thai orchid, Dendrobium draconis, possesses various pharmacological activities; however, its effect on cancer apoptosis was not investigated before. This study demonstrates for the first time that GG induced lung cancer cells apoptosis which was prevented by the addition of Z-VAD-FMK, caspase 3 inhibitor. Western blot analysis reveals that anti-apoptotic Bcl-2 and Mcl-1 were dramatically downregulated, in concomitance with an upregulation of proapoptotic Bax protein in response to GG treatment. Anti-apoptosis FLIP was not significantly changed, suggesting that GG -mediated apoptosis was through mitochondrial-dependent mechanism. Interestingly, the fact that GG showed no cytotoxic effect on normal keratinocyte Hacat cells, supports its selectivity on cancer cells. This finding sheds light on an anticancer activity of GG, providing an evidence for development of this agent for cancer therapy.