Honokiol, a natural product from Magnolia officinalis, has been used in traditional Chinese and Japanese medicine for the treatment of various ailments due to its various pharmacological activities, including anti-inflammatory and anti-oxidant properties. Lung cancer is the leading cause of cancer related deaths in both men and women in the United States and worldwide. As one of every three cancer-related deaths is attributable to lung cancer, and the dismal 5-year survival rate of approximately 14% has shown no improvement over the past three decades, it is therefore desired to develop newer and effective chemopreventive or chemotherapeutic agents and strategies to address this public health issue. We examined the chemotherapeutic potential of honokiol on various human non-small cell lung cancer (NSCLC) cells in vitro. The selection of NSCLC cell lines was based upon the fact that NSCLC represents approximately 80% of all types of lung cancer and includes squamous cell carcinomas, adenocarcinomas and large-cell carcinomas. Here, we report that in vitro treatment of human NSCLC cells (A549, H1299, H226, H460, H1975 and H157) with honokiol inhibited cell proliferation and induced cell death in a dose- (10-50 µM) and time-dependent (24 h-72 h) manner. Treatment of normal human bronchial epithelial cells (BEAS-2B) with honokiol under identical conditions did not significantly affect their viability. The honokiol-induced inhibition of proliferation of NSCLC cells was associated with G0/G1 phase arrest, which was associated with the inhibition of expression of cyclins D1, D2 and E, and cyclin-dependent kinase (Cdk) 2, Cdk4 and Cdk6 proteins, increased expression of the cyclin kinase inhibitory proteins (Cip1/p21 and Kip1/p27). Honokiol also significantly (p<0.05-0.001) enhanced apoptosis of NSCLC cells with induction of a higher ratio of Bax/Bcl-2 proteins, disruption of mitochondrial membrane potential, and activation of caspase-3, and poly (ADP-ribose) polymerase. Pretreatment with the pan-caspase inhibitor, z-VAD-fmk, significantly blocked the honokiol-induced apoptosis, as also confirmed by the comet assay analysis of DNA fragmentation, suggesting that honokiol-induced apoptosis of human NSCLC cells is mediated primarily through the caspase-dependent pathway. The effectiveness of honokiol in checking the growth of NSCLC cells without affecting the growth of normal bronchial epithelial cells indicates that honokiol may be a promising candidate for non-small cell lung cancer therapy.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2975.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

American Association for Cancer Research
2009