title: Comparative evaluation of small-molecule chemosensitizers in reversal of cisplatin resistance in ovarian cancer cells.
abstract: Cisplatin-resistance is one of the major challenges in the treatment of epithelial ovarian cancer. Small-molecule chemosensitizers provide a therapeutically feasible approach to overcome cisplatin resistance in ovarian cancer. However, proper selection of chemosensitizer is of prime importance owing to phenotypic differences in cisplatin-resistant ovarian cancers. The resistance reversal activity of chemosensitizers buthionine sulfoximine (BSO), triethylenetetramine (TETA), genistein, rapamycin and colchicine was investigated in various cisplatin-resistant ovarian cancer cells, 2008 C13, CP70 and OVCAR 8 using MTT assays. Cellular accumulation of cisplatin in the presence of chemosensitizers was analyzed by inductively-coupled plasma-mass spectroscopy (ICP-MS). Chemosensitizers exhibited resistance reversal activity in 2008 C13 and CP70 cells in the following order; colchicine> genistein>TETA> rapamycin ≥ BSO (p<0.05), which is in correlation with cellular accumulation of cisplatin. In conclusion, our study demonstrates that resistance reversal activity of chemosensitizers varies with phenotypic behavior of cisplatin-resistant ovarian cancer cells. Data from our study can be utilized to choose a specific chemosensitizer for individualized combination therapy for cisplatin-resistant ovarian cancer.
authors.affiliation: Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX 78363, USA.
authors.forename: Venkata K
authors.initials: VK
authors.lastname: Yellepeddi
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Vangara
authors.forename: Ajay
authors.initials: A
authors.lastname: Kumar
authors.forename: Srinath
authors.initials: S
authors.lastname: Palakurthi
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D019328:Buthionine Sulfoximine / Q000008:administration & dosage / Q000494:pharmacology; D016466:CHO Cells; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D003078:Colchicine / Q000008:administration & dosage / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage / Q000494:pharmacology; D013058:Mass Spectrometry / Q000379:methods; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D020123:Sirolimus / Q000008:administration & dosage / Q000494:pharmacology; D014266:Trientine / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D007529:Isoflavones; C040641:genistin; D019328:Buthionine Sulfoximine; D002945:Cisplatin; D014266:Trientine; D003078:Colchicine; D020123:Sirolimus