(697b) Novel Inclusion Complexes for Cancer Treatment. an Approach Based on Energetics Metabolism

Cancer is considered as one of the illness that causes a great amount of deaths each year in developing countries. From several years, cancer treatment has been focused on drugs that interact with DNA or other proteins that are involved in cell division and replication. However, the main drawback of that treatment was the no-selectivity of the treatment, affecting equally healthy and tumor cells. Nevertheless, differences in how tumor cells produce energy has been discovered from the study of their metabolism during last years. Those differences have been named as Warburg effect. It has been proved that tumor cells produces energy preferentially by pentose phosphate pathway, which is a way of minor importance in healthy cells. Based on those differences, a new way for treatment can be opened if pentose phosphate pathway is blocked selectively.

In this work, an inclusion complex based on cyclodextrin and a steroid is prepared so as to block that pathway. Specifically, it reduces the activity of the first enzyme in the pathway (glucose-6-phosphate dehydrogenase). Inclusion complex was prepared successfully with a yield greater than 80% and its effect was tested “in vitro” in 8 different cell lines: 6 tumor cell lines (liver, lung, breast, ovary, colorectal and prostate) and 2 healthy cell lines (fibroblast and kidney). Results show that the complex designed is able to reduce significantly cell viability (measured by MTT assay) in all tumour cell lines, and without significant effect in healthy ones. That selectivity suggests a new alternative for tumour treatment. Moreover, other experiments were carried out so as to quantify the effect on cell metabolism, and results show a reduction in G6PD activity and a modification in the level of ROS (reactive oxygen species) inside the cell. Furthermore, the differences between effectiveness along the different types of cells lines was also related with expression levels of sugar transports and the relative expression of the enzyme inhibited. That correlation may allow setting a dose of the treatment depending on the tissue.

Summing up, a new system for cancer treatment was developed, with a wide range of action, and with high levels of selectivity so as to reduce the undesirable side effects.