| Breast cancer is one of the leading causes of cancer death in American women and unfortunately, current chemotherapy protocols still have limitations: (1) most chemotherapy destroys not only cancer cells, but also many rapidly dividing normal cells and (2) cancer cells can develop resistance to chemotherapeutic agents through mutation. Thus, there is a crucial need to find new chemical agents which (1) exploit differences between normal cells and breast cancer cells in order to selectively kill the breast cancer cells and (2) provide new, complementary chemotherapeutic techniques to be used in conjunction with other breast cancer treatments or in combination with other anticancer drugs. Tropical rainforest plants have evolved chemical defensive mechanisms to avoid herbivory and resist pathogens. Zanthoxylum is a genus of about 250 species in Rutaceae that contain a rich source of lignans, alkaloids, coumarins, amides, flavonoids, terpenes and other metabolites with pharmacological properties. Therefore, there are beneficial novel chemical agents present in Zanthoxylum that can be studied for human maladies, such as cancer. In this work, the fractionation of active materials, screening of cytotoxicity, determination of isolated chemical structures, and binding energies of human DNA topoisomerase I of Zanthoxylum setulosum were evaluated. Zanthoxylum setulosum was notably cytotoxic (100% kill at 100 microg/ml) on MCF-7, MDA-MB-231, and MDA-MB-468 cells in vitro. The cytotoxic effects of isolated compounds from Zanthoxylum setulosum were tested against MCF-7 and MDA-MB-231 breast cancer cell lines. Chemical structures of cytotoxic compounds were determined through NMR, HPLC, and X-ray crystallography spectroscopic techniques. Lupeol, sesamin, lichexanthone, and sesquichamaenol were isolated from Zanthoxylum setulosum. Lupeol exhibited high cyctotoxic killing against MCF-7 and MDA-MB-231 cells at 100% kill at 100 mg/ml, with a LC50 value of 85.3 microM and 453.9 microM, respectively. Molecular docking studies for binding energies of lichexanthone with five DNA structures, PDB: 1k4t, 1z3f, 1al9, 1t8i, and 1sc7 were calculated using ArgusLab and Molegro Virtual Docker. The primary objective was to isolate fractions from Zanthoxylum setulosum and identify the active components and mechanism for new potential chemotherapeutic drugs. |
