Date of Award
1-1-2016
Document Type
Dissertation
Degree Name
Ph.D. in Pharmaceutical Sciences
Department
Biomolecular Sciences
First Advisor
Kristine L. Willett
Second Advisor
Asok K. Dasmahapatra
Third Advisor
John M. Rimoldi
Relational Format
dissertation/thesis
Abstract
Saffron extract and its active constituents were evaluated as chemopreventatives and/or treatments for prostate cancer. Different models of prostate cancer (in vitro and in vivo) were used for studying saffron and its constituents’ mechanisms. In normal prostate cells, saffron extract, crocetin, and safranal, in non-toxic concentrations, possessed antioxidant properties against the reactive oxygen species induced by H2O2 which further supports saffron constituents as chemopreventative agents. Moreover, saffron and its active constituents produced cytotoxicity in prostate cancer cells through intrinsic apoptosis pathways. Potential efficacy in minimizing prostate cancer metastasis was also examined. Saffron extract, crocetin, and safranal decreased the migration and invasion capability of prostate cancer cells in vitro. Among all tested agents, safranal caused the lowest cytotoxicity in normal prostate cells. A new HPLC analytical method was developed to simultaneously measure saffron marker compounds (picrocrocin, crocin, safranal, and crocetin), which can be used to assess the quality and to identify adulteration of saffron samples. Our study emphasized the importance of standardizing the solvent systems used during extraction to minimize cytotoxicity in normal cells. The saffron available commercially differed greatly based on their constituents’ concentrations and biological activity, even when the plants came from the same region of cultivation, making it essential to evaluate each batch chemically and biologically. To overcome the limitations of current mammalian models, a xenograft zebrafish model for prostate cancer was developed as a new alternative. A zebrafish transgenic line was created in our laboratory which offered unique characteristics, including physical transparency and vasculature system fluorescence. Our study optimized procedures for transplanting cancer cells into zebrafish and was validated using docetaxel as a known chemotherapy for prostate cancer. In conclusion, the optimized HPLC analytical method is an excellent tool for saffron quality evaluation. Saffron extract and its active constituents are considered good candidates as a chemopreventative and treatment for prostate cancer. The transgenic zebrafish in vivo model minimizes the time needed in preclinical evaluations of new medications and offers the potential for personalization of treatment options based on each patient’s case.
Recommended Citation
Albaqami, Faisal Fayih, "Saffron extract and its active constituents as preventative and/or treatment agents for prostate cancer using in vitro and in vivo models" (2016). Electronic Theses and Dissertations. 1468.
https://egrove.olemiss.edu/etd/1468