Molecular Mechanisms of y-Oryzanol Against Non-Small Cell Lung Cancer

Abstract

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, which is the leading cause of cancer death, with an increasing prevalence every year. Specific treatments for some of the multiple kinds of NSCLC have been developed, but their efficacy is low and they are not applicable to all types. Cell viability experiments suggested that rice bran oil could be a source of anti-carcinogenic phytochemicals against NSCLC. γ-Oryzanol is the major component in rice bran oil and has anti-cancer properties on various prostate cancer cell lines and in some animal models. The goal of this study was to determine whether the most abundant components in the γ-oryzanol mixture (24-mCAF, CAF, CMF and β-SF) have cytotoxic activity against A549 cells, a NSCLC cell line. The effect of these compounds on cell proliferation was tested using the colorimetric methylthiazol tetrazolium (MTT) assay. Among all four compounds, 24-mCAF showed the strongest inhibitory effect on cell proliferation of A549 cells, while β-SF did not seem to affect it. An iTRAQ-based quantitative proteomics analysis combined with Ingenuity Pathway Analysis (IPA) revealed that the changes in the proteome caused by 24-mCAF were consistent with cancer inhibition. Cell death and apoptosis were activated and cell proliferation was inactivated. Myb binding protein 1A is a tumor suppressor protein that binds to several transcription factors. The results obtained in this study indicate that 24- mCAF induces MYBBP1A up-regulation, which contributes to stop cancer progression through different mechanisms. These mechanisms include its interaction with P53, which induces apoptosis and cell cycle arrest; its interaction with NFкB, which inhibits inflammatory processes; and its interaction with SIRT6, which regulates the expression of several cancer-related proteins. Up-regulation of MYBBP1A by 24-mCAF was verified with western blot and the results were consistent with those obtained with iTRAQ. This study provides the first step for understanding the effect of γ-oryzanol on A459 cells at the cellular and molecular level, providing a possible candidate for NSCLC treatment or prevention.