Collateral sensitivity of natural products in drug-resistant cancer cells.

摘要: Cancer chemotherapy is frequently hampered by drug resistance. Concepts to combine anticancer drugs with different modes of action avoid the development resistance did not provide expected success in past, because tumors can be simultaneously non-responsive many (e.g. multidrug phenotype). However, may specifically hypersensitive other - a phenomenon also termed collateral sensitivity. This seems general biological mechanism, since it occurs drug-resistant Escherichia coli and Saccharomyces cerevisiae. Here, we give timely comprehensive overview on hypersensitivity resistant cancer cells towards natural products their derivatives. Since majority clinically established are or one way another derived from them, worth hypothesizing that deliver promising lead compounds for sensitive drugs. Hypersensitivity only classical ABC transporter-mediated resistance, but phenotypes. Resistant cancers diverse classes origins (i.e. mitotic spindle poisons, DNA topoisomerase 1 2 inhibitors, phytochemicals isolated medicinal plants, (semi)synthetic derivatives phytochemicals, antibiotics, marine drugs, recombinant therapeutic proteins others). Molecular mechanisms sensitivity include (1) increased ATP hydrolysis reactive oxygen species production futile cycling during efflux, (2) inhibition production, (3) alterations target expression topoisomerases heat shock proteins, Wnt/β-catenin pathway, mutations β-tubulin). The needs exploited clinical oncology novel combination protocols exhibit high degrees tumors.