title: Reversal effects of components from the fruits of Illicium simonsii on human Adriamycin-resistant MCF-7 and 5-fluorouracil-resistant Bel7402 cells.
abstract: Twenty-one compounds including seven characteristic sesquiterpene lactones were isolated from Illicium simonsii and screened in vitro for their potential to restore the sensitivity of Adriamycin (ADR) resistant breast cancer cells (MCF-7/ADR) and 5-fluorouracil-resistant hepatocellular carcinoma cells (Bel7402/5-FU) to ADR and 5-fluorouracil, respectively. These compounds were found to be non-toxic to a panel of tumour cell lines: human breast cancer cells (MCF-7), cervical cancer cells (HeLa), hepatic liver carcinoma cells (HepG-2, Bel7402) and gastric carcinoma cells (BGC-823, SGC-7901). Five compounds showed an obvious decrease in the IC(50) of doxorubicin in MCF-7/ADR and four compounds sensitized Bel7402/5-FU to 5-fluorouracil at non-toxic concentrations. The relationship between the structure of these non-cytotoxic substances and their multidrug-resistant (MDR) reversal abilities was investigated by principal component analysis (PCA) of the reversing fold (RF) values of these compounds and their calculated molecular descriptors of the tested substances. No correlations were found between the reversal potencies of these compounds to the two MDR cells. Compounds with lower polarity generally had stronger sensitizing ability to the P-glycoprotein (Pgp) overexpressed MCF-7/ADR cells. On the other hand, higher hydrophilic compounds seemed to exhibit a stronger reversal effect to the MDR-associated protein (MRP) overexpressed Bel7402/5-FU cell line. Our findings favoured further investigations on the active substances and the underlying mechanisms.
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, PR China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Wei
authors.forename: Jun-Song
authors.initials: JS
authors.lastname: Wang
authors.forename: Ling-Yi
authors.initials: LY
authors.lastname: Kong
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000737:chemistry; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000494:pharmacology*; D005638:Fruit / Q000737:chemistry*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D029523:Illicium / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D025341:Principal Component Analysis; D013329:Structure-Activity Relationship
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D004317:Doxorubicin; D005472:Fluorouracil