title: Cytotoxic activity of artemisinin derivatives against cholangiocarcinoma (CL-6) and hepatocarcinoma (Hep-G2) cell lines.
abstract: Cytotoxic activity of artemisinin and derivatives in the presence and absence of holo-transferrin and expression of genes involved in resistance of cancer cells were investigated in human cholangiocarcinoma (CL-6) and hepatocarcinoma (Hep-G2) cell lines in vitro. After incubation with the test drugs and 5-fluorouracil (5-FU) cytotoxicity was asessed by MTT assay. RNA was extracted after 24 hour exposure to holo-transferrin for invesstigation of the expression of transferrin receptor 1 (TDR1), multidrug resistance 1 (MDR1), multidrug resistance protein 1 (MRP1), multidrug resistance protein 2 (MRP2), and multidrug resistance protein 3 (MRP3). The median IC₅₀ of artemisinin, artesunate, artemeter, dihydroartemisinin and 5-FU were as follows: CL-6: 339, 131, 354, 75, and 377 microM, respectively; Hep-G2: 268, 50, 233, 29, and 1,380 microM. Exposure to holo-transferrin had no influence on sensitivity of either cell line to artemisinin derivatives, but resulted in a 3-fold increase in the expression of TR1 and MDR1, and a 2-fold increase in the expression of MRP1 and MRP2 in CL-6 cells. With Hep-G2, a 3-fold increase in the expression of MDR1 and MRP3 and a 2-fold increase in expression of MRP2 were observed. Dihydroartemisinin exhibited the most potent cytotoxic activity against both cell lines and holo-transferrin caused different patterns of expression of resistance-associated genes.
authors.affiliation: Pharmacology and Toxicology Unit, Graduate Program in Biomedical Sciences, Thammasat University, Bangkok, Thailand.
authors.forename: Wanna
authors.initials: W
authors.lastname: Chaijaroenkul
authors.forename: Vithoon
authors.initials: V
authors.lastname: Viyanant
authors.forename: Wiratchanee
authors.initials: W
authors.lastname: Mahavorasirikul
authors.forename: Kesara
authors.initials: K
authors.lastname: Na-Bangchang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D037621:Artemisinins / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D011990:Receptors, Transferrin / Q000096:biosynthesis / Q000235:genetics; D014168:Transferrin / Q000494:pharmacology
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015703:Antigens, CD; D000970:Antineoplastic Agents; D037621:Artemisinins; C068126:CD71 antigen; D011990:Receptors, Transferrin; D014168:Transferrin; C110714:holotransferrin; C039060:artenimol; D005472:Fluorouracil