Effects of Prodigiosin on Breast Cancer Cell Viability

Darh, Karmaseh (2016-07-22)


The Luteinizing Hormone-releasing Hormone (LHRH); also known as a Gonadotropin-Releasing Hormone can be utilized for targeted therapy with cytotoxic analogs, in which prodigiosin is linked to the [D-Lys6] LHRH. Our studies demonstrate receptor-mediated actions of the cytotoxic LHRH analog in LHRH receptor positive breast cancer cells. Chemotherapy today is the only systematic therapy for patients with triple negative breast cancer cells. About 50% to 64% of human breast cancer expressed receptors for LHRH might be used as a target. This thesis focused on a new conjugate in which prodigiosin was used as a cytostatic compound and an analog or Luteinizing Hormone-releasing Hormone (LHRH) as a targeting moiety was synthesized. The molecules of the peptide were modified to allow its connection to the prodigiosin via a spacer. The objectives of our study were to synthesize a bioconjugate of LHRH analog [D-Lys]-LHRH and prodigiosin targets and inhibits breast cancer cell growth in vitro and in vivo. Prodigiosin was synthesized by bacteria (Serratia marcescens (subsp. marcescen)). High-performance liquid chromatography (HPLC) analysis on the purity was determined to be 92.8% and the ultraviolet (UV) reading was 535nm. Adhesion force measurements were also carried out to determine the adhesion force between the conjugate and the breast cancer cells. This had the highest measurement as compared to the bare, prodigiosin coated and LHRH-coated tips. The adhesion force of the conjugates measured (80±4nN) which gave the highest peak. The conjugates were prepared linking prodigiosin through its 14-0-hemiglutarate to [D-Lys6] LHRH. The results showed that the use of LHRH peptide as a targeting moiety in the anticancer drug delivery substantially enhanced the efficacy of prodigiosin which leads to amplified apoptosis induction in the tumor and minimized the side effects of the anticancer drug on healthy organs. In conclusion, prodigiosin conjugate with LHRH exhibited an antiproliferative effect for which its further testing will be implemented.