Mechanisms of Apoptotic Effects Induced by Resveratrol, Dibenzoylmethane, and Their Analogues on Human Lung Carcinoma Cells

Abstract

While lung cancer accounts for approximately 20% of cancer diagnoses, it is the leading cause of tumor-related deaths. The apoptotic effects of 3,5,4'-trihydroxystilbene (resveratrol), dibenzoylmethane (DBM), and their analogues on human lung cancer cells are generally unclear. The aims of this study were to evaluate the apoptotic effects and molecular mechanisms of resveratrol, DBM, and their analogues on human lung cancer cells. The results of the MTT and lactate dehydrogenase (LDH) leakage assays indicated that resveratrol, 3,5,4'-trimethoxy-trans-stilbene (MR-3), and 1-(2-hydroxy-5-methylphenyl)-3-phenyl-1,3-propanedione (HMDB) could inhibit cell population growth and induce cell injury in A549 and CH27 cell lines. Resveratrol and HMDB could induce apoptotic cell death in the A549 and CH27 cell lines. Moreover, cellular growth of the A549 and CH27 cell lines might be inhibited by MR-3 through induction of apoptosis and regulation of the cell cycle. The A549 and CH27 cell lines treated with resveratrol, MR-3, and HMDB showed a time-dependent reduction of mitochondrial membrane potential, and the Bax/Bcl-2 ratio increased gradually with a higher concentration of polyphenols. The resveratrol-, MR-3-, and HMDB-induced apoptosis in the A549 and CH27 cell lines were controlled through activation of caspase-9 and caspase-3 and subsequent cleavage of PARP. In conclusion, we have demonstrated that resveratrol, DBM, and their analogues could be effective candidates for chemoprevention of lung cancer and HMDB might have the strongest ability for inducing apoptosis.