Abstract #3676: Antroquinonol inhibits tumorgenesis and metastasis in highly invasive non-small-cell lung cancer cells

Antrodia camphorata , a parasitic fungus indigenous to Taiwan, has been used as the folk medicine in immuno-regulation and anti-cancer therapies for over six decades. Recently, antroquinonol, an ubiquinone derivative from Antrodia camphorata , has been reported with the selective cytotoxicity in several cancer cell lines, however, the molecular mechanisms in anti-cancer were unclear. In this study, we found that antroquinonol could inhibit cell proliferation in highly invasive non-small-cell lung cancer (NSCLC) cells (IC50=0.8 \#956;g/ml in A549 cells and IC50=1.4 \#956;g/ml in CL1-5 cells), but has no significantly cytotoxic effects on normal human airway epithelial BEAS2B cells. The colony formation assay also indicated that antroquinonol could significantly reduce tumorgenesis at concentration 0.3 \#956;g/ml. The cancer cell migration and invasion were reduced by antroquinonol in a concentration-dependent manner (0.1-3.0 \#956;g/ml). To study the potential mechanisms in anti-tumorgenesis and metastasis, the antroquinonol-regulated gene expression profiles were determined using human HG-U133 Plus 2.0 Gene Chip (Affymetrix), the differentially expressed genes were further performed to the Complex Regulation Prediction Database (CRPD) for pathway enrichment analysis; the results showed that a cluster of metastasis-related genes (e.g., Integrin, alpha V beta 1, vav3 and met oncogenes, and Rho GTPase) and the Jak-Stat signaling pathway-related genes, including the epidermal growth factor receptor (EGFR) signaling, mitogen-actived protein kinase (MAPK), and cell cycle-related genes, were highly regulated by antroquinonol. The real time quantitative RT-PCR confirmed that the focal adhesion-related and Jak-Stat signaling pathway-related molecules were significantly regulated by antroquinonol, including ATM (2.32 folds reduced), SKP2 (2.85 folds reduced), MAP4K3 (3.14 folds reduced), MAP3K7 (1.47 folds reduced), MAP2K1IP (2.47 folds reduced), integrin alpha V (1.86 folds reduced) and IL6ST (3.24 folds reduced). Immunoblotting analyses showed that the EGF-stimulated EGFR, AKT, and ERK phosphorylations were significantly reduced by antroquinonol. In conclusion, these results showed that the new anti-cancer compound, antroquiononol, could inhibit cancer cell growth, inhibit cancer cell migration and invasion, reduce cell survival signaling selectively in the highly invasive lung adenocarcinoma cells. We suggested that antroquinonol might have the potential to be the novel leading compound in new anti-cancer drug developing for NSCLC treatment. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3676.