Nanonoscapine: A Promising Treatment for Prostate Cancer Through Targeting GLI1 and BAX Expression

Abstract

Abstract Noscapine as an opium-derived phthalide isoquinoline alkaloid has been revealed with anti-turmeric impacts by various mechanisms. Attending to the lower side effects of nano-drugs and their delivery benefits, nanonoscapine is expected to disclose better features. In this study, MTT assay and flow cytometry were performed and revealed that the 50 µg/ml concentration during 48h treats prostate cancer cells appropriately, causing the G2/M arrest and apoptosis. Gene expression analysis using RNA sequencing illustrated a correlation between cancer cell progression and GLI1 and BAX suppression. Also, using qRT-PCR, it was observed that nanonoscapine upregulates GLI1 and BAX in cancer cells. Through computational and Bioinformatics analysis, GLI1 overexpression by nanonoscapine was revealed to disrupt nuclear division during mitosis and arrest cells at the G2/M phase by suppressing the expression of CDK1 and inducing the expression of IRAK3. Besides, BAX upregulation by nanonoscapine was detected to enhance GSK3A and BID expressions which foster BAX function in permeabilizing mitochondrial outer membrane and releasing cytochrome c which leads to apoptosis. Moreover, the Kaplan Meier plot for GLI1, BAX, IRAK3, CDK1, GSK3A, and BID indicated that nanonoscapine can improve prostate cancer patients’ survival times. Nanonoscapine can be used instead of noscapine besides chemotherapy to treat prostate cancer since it targets cancer cells and improve patients’ overall survival.