title: Mithramycin inhibits etoposide resistance in glucose-deprived HT-29 human colon carcinoma cells.
abstract: Physiological cell conditions such as glucose deprivation and hypoxia play roles in the development of drug resistance in solid tumors. These tumor-specific conditions cause decreased expression of DNA topoisomerase IIalpha, rendering cells resistant to topo II target drugs such as etoposide. Thus, targeting tumor-specific conditions such as a low glucose environment may be a novel strategy in the development of anticancer drugs. On this basis, we established a novel screening program for anticancer agents with preferential cytotoxic activity in cancer cells under glucose-deprived conditions. We recently isolated an active compound, AA-98, from Streptomyces sp. AA030098 that can prevent stress-induced etoposide resistance in vitro. Furthermore, LC-MS and various NMR spectroscopic methods identified AA-98 as mithramycin, which belongs to the aureolic acid group of antitumor compounds. We found that mithramycin prevents the etoposide resistance that is induced by glucose deprivation. The etoposide-chemosensitive action of mithramycin was just dependent on strict low glucose conditions, and resulted in the selective cell death of etoposide-resistant HT-29 human colon cancer cells.
authors: Korea Research Institute of Bioscience and Biotechnology, Yusong, Daejeon 305-806, Korea.
authors: Eun-Mi
authors: EM
authors: Lee
authors: Hae-Ryong
authors: HR
authors: Park
authors: Ji-Hwan
authors: JH
authors: Hwang
authors: Dong-Jin
authors: DJ
authors: Park
authors: Kyu-Seob
authors: KS
authors: Chang
authors: Chang-Jin
authors: CJ
authors: Kim
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D008926:Plicamycin / Q000494:pharmacology*
chemical_list: D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D005947:Glucose; D008926:Plicamycin