Proteomic profiling the molecular signatures of plectranthoic acid in prostate cancer cells.

Among cancers, prostate cancer (PCa) is frequently detected solid tumor and a growing problem for the male population, globally. Newer treatment modalities with specific targets are required for management. Plant-derived agents/drugs have historically been useful in cancer therapeutics. Natural metabolite i.e. plectranthoic acid (PA), inhibits the proliferation of PCa cells and has potent anti-cancer potential. Herein, we aim to identify the molecular signatures of PA. Proteins from control and PA-treated PCa cells were analysed using high-throughput labeled free proteomics approach. Data was processed with the SIEVE software and thoroughly analysed by using Ingenuity pathway analysis (IPA) and PANTHER. A total of 98 unique peptides, showing >2 fold change, were identified. Results indicated that PA modulates oncogenic pro-survival and pro-apoptotic signaling pathways in PCa cells. mTOR was the major canonical pathway targeted by PA, the inhibition of which was likely to induce PA mediated apoptosis. Moreover, PA interacts with the rapamycin binding domain of mTOR, demonstrated by the molecular dynamic (MD) simulation and binding free energy calculations. Furthermore, the biological process moderated by PA with a high percentage was a metabolic process. Taken together, PA appears to have pleiotropic effects, as it modulates multiple key signaling pathways, supporting the potential usefulness. SIGNIFICANCE: Studies on the mechanism of action of therapeutic agents are crucial for drug development. These studies support the selection of a therapeutic agent, appropriate models of its efficacy, and designing of further experiments. Furthermore, information on mechanism of action may suggest strategies for combination therapies. In this regard Proteomics provide the platform for comprehensive understanding of the molecular action mechanisms of newly discovered therapeutic agents. Current research highlights the new insights into mode of action of novel therapeutic metabolite i.e. Plectranthoic acid (PA). Using labeled free proteomics approach we extracted the underlying mechanisms for the anticancer activity of PA using prostate cancer model. The result of the study will pay the way for further investigations on this potent natural compound in different cancers and will provide a root for its development as a lead.