ABSTRACT
In the present study, chitin specific lectin was purified from fruit exudates of Praecitrullus fistulosus. The lectin was purified and analyzed using affinity chromatography, RP-HPLC and electrophoretic studies. Furthermore, protein was identified by MALDI-MS/MS and peptide mass fingerprinting. Purified lectin (PfL) effectively agglutinates RBC, lymphocytes and displayed strong cytotoxicity against colon cancer (line HT29) cells among screened cells. PfL induced apoptosis by altering the expression of apoptotic proteins via caspadse-3 dependent pathway. In vivo studies using EAC mice model proves the efficacy of PfL by activating apoptosis and inhibiting the tumor neovasculature by targeting the MVD, VEGF and MMP's secretion. More importantly, the PfL treatment leads to effective inhibition of tumor growth and a â¼2.71 fold increase in the lifespan of EAC mice. Collectively, our study provides comprehensive evidence that the role of dietary lectins with significant cytotoxic potential by targeting tumor angiogenesis and activating apoptosis in cancer study models.
Subject(s)
Angiogenesis Inhibitors/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Carcinoma, Ehrlich Tumor/drug therapy , Chitin/chemistry , Cucurbitaceae/chemistry , Lectins/pharmacology , Neovascularization, Pathologic/drug therapy , Angiogenesis Inhibitors/chemistry , Angiogenesis Inhibitors/isolation & purification , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Carcinoma, Ehrlich Tumor/metabolism , Carcinoma, Ehrlich Tumor/pathology , Cell Proliferation/drug effects , Disease Models, Animal , Fruit/chemistry , Humans , Lectins/chemistry , Lectins/isolation & purification , Mice , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Tumor Cells, CulturedABSTRACT
The objective of this study was to compare the effectiveness of intramuscular sustained release Pluronic F127 (PF127) gel formulations of deslorelin, a potent GnRH agonist, and GnRH to their solution formulations in inducing the release of luteinizing hormone and formation of luteal tissue in cattle. Injectable gel formulations of deslorelin and GnRH were prepared using Pluronic F127 (25%, w/w), a block copolymer. PF127 gels sustained the in vitro release of deslorelin as well as GnRH at similar rates and reduced drug degradation in muscle tissue when compared to the solution formulations. Deslorelin, as well as GnRH, elicited desirable elevations in plasma LH and progesterone concentrations in vivo. When compared to the solution formulations, the gel formulations of both drugs induced a broader peak of LH. Also, the peak LH levels were lower and the peak times were delayed with the gel formulations compared to the solution formulations. While the solution dosage form of deslorelin and GnRH elicited similar responses, the PF127 gel formulation of deslorelin induced peak LH levels at an earlier time (3 h for deslorelin versus 5.25 h for GnRH). The results indicate that, deslorelin exerts a pharmacological effect in cattle. The LH response to deslorelin as well as GnRH can be altered by controlling the input or the release rate of the drug. PF127 gel formulations can sustain peptide release and reduce peptide degradation.
