Institution: Universidad Central del Caribe

Email: yancy.ferrer@uccaribe

Translational research studies of phytochemicals have been ongoing for decades, providing important clinical outcomes. These studies led to the discovery of many therapeutic drugs, and almost half of the drugs available on the market are naturally derived compounds. Nutritional and over-the-counter supplements are the most accessible phytochemicalbased medications for the general population, especially those who cannot afford medical insurance. Many of these supplements are not uniformly prepared or characterized well enough to have an effective clinical dose against cancer. There is also a gap in knowledge on the phytochemical's effects on acquired drug resistance and metastasis in tumor progression. Therefore, we have a critical need to generate standardized, efficient preparations of phytochemicals and to study if these can induce specific genetic changes that influence chemoresistance and metastasis in cancer. The project's long-term goal is to systematically develop and characterize the anti-chemoresistance and anti-metastatic potential of our standardized aqueous nanoparticle suspensions made from traditional plants with anticancer phytochemicals. In the proposed studies, we selected three phytochemical-rich plants: oregano, cinnamon and graviola; and one type of cancer (non-small cell lung carcinoma; NSCLC). These nanosuspensions (NS) will be tested for their effectivity alone and combined with the gold-standard treatment for NSCLC, cisplatin (CisPt). This pilot project's objective is to determine the anticancer effect of known phytonutrients in nanosuspensions, focusing on preventing chemoresistance and metastatic spread, by quantifying the genes they modify in NSCLC. The rationale of our study is that interactions between primary metabolites (i.e., proteins, lipids, and carbohydrates) and secondary metabolites (i.e., phytochemicals) in phytonutrients induce a natural behavior for all these molecules to generate a nanosuspension (NS). Based on this, we hypothesize that, specifically in the NS form, phytonutrients will have better absorption and will work synergistically with CisPt, increasing its effectivity by reducing expression of chemoresistance and metastasis promoting genes. We expect these combinations to work as adjuvant therapies to reduce the chemo-sessions  patients undergo and decrease toxic side effects. To test our hypothesis we propose: 1) To determine gene expression of NSCLC cells exposed to the NS; 2) To determine tumor growth, and gene expression after oral administration o f the phytonanosuspensions to a lung carcinoma mouse model. The expression of chemoresistance and metastasis genes will be measured by qRT-PCR and performed in the presence and absence of CisPt. Results will impact the field of lung cancer therapy confirming the potential of our phyto-NS as adjuvant therapies against drug resistance and metastasis.