BIO087 Evaluation of cytotoxicity and apoptosis induction of Oxo-monastrol in human hepatoma cell line C3A.

Abstract

Chemotherapeutic agents used for cancer treatment have as one of their principal aims mitosis arrest. Despite the great advances obtained in cancer treatment with these agents is necessary to obtain new substances having different targets of not microtubules in order to reduce side effects and thus optimize chemotherapy and quality of life those in need. With the understanding of cell cycle and its chemical mediators began the search for new targets for anti-mitotic not involving the microtubules, thereby preventing some side effects such as neurotoxicity. Kinesins stood out in this quest. Among the motor kinesins related to mitosis, the protein EG5 has been studied for their potential for cancer therapy because of its importance for cell division. This protein is overexpressed in tumor cells compared to non-tumor cells. Due to the specificity of Monastrol to act on targets that are specific to tumor cells, were developed some analogues of this compound in order to enhance its effect and understand its mechanism of action. One of these analogues is the Oxo-monastrol, a precursor of Monastrol which the sulfur atom was replaced by an oxygen atom. It is believed that this analog, as well as monastrol, inhibits EG5 motor activity by allosteric inhibition which prevents ATP, no movement of centrossomos toward the poles, the spindle pole is not formed, and then, the cell is arrested in G2-M phase of cell cycle and is programmed cell death (apoptosis).