title: Short-term serum deprivation confers sensitivity to taxanes in platinum-resistant human ovarian cancer cells.
abstract: BACKGROUND
  Based on the evidences showing that serum deprivation provokes apoptosis in a variety of cells, we have investigated the effect of serum deprivation on drug sensitivity.
  
  
  METHODS
  After human ovarian cancer cells were preincubated in 0.5 % serum containing medium for 12 hours, cellular drug sensitivities were determined by colony-forming assay.
  
  
  RESULTS
  Serum deprivation treatment resulted in significant increase in paclitaxel sensitivity by factors of mean ± SD, 148.6 ± 28.1 and 10.1 ± 1.0 (n = 3; P < 0.001) fold in platinum-resistant C13 and CP70 cells, respectively. Similarly, serum deprivation induced significant docetaxel sensitivity in these cell lines. However, no enhancement effect of serum deprivation was observed in platinum-sensitive 2008 and A2780 cells. Serum deprivation did not have any effect on the sensitivities to cisplatin, vincristin, and doxorubicin in all of these cells. More than 7-fold increase of apoptotic cells were observed in C13 or CP70 cells when they were treated by serum deprivation followed by paclitaxel compared with the treatment of either serum deprivation or paclitaxel alone. Confocal laser microscopy using rhodamine 123 and flow cytometric analysis with 3,3'-dihexyloxacarbocyanine iodide revealed that serum deprivation decreased mitochondrial membrane potential in C13 or CP70 cells, whereas no change was observed in 2008 and A2780 cells. This indicates that serum deprivation induced depolarization specifically in platinum-resistant cells. Electron microscopy revealed that serum deprivation caused regeneration of mitochondrial matrix structure in C13 or CP70 cells where mitochondria were usually destructed and disappeared.
  
  
  CONCLUSIONS
  These results indicate that serum deprivation confers taxane hypersensitivity specifically in platinum-resistant cells by recovering their impaired mitochondrial functions. The evidence might be clinically beneficial for the development of new chemotherapeutic technology, particularly for the patients with platinum-resistant ovarian cancer.
authors.affiliation: Department of Obstetrics/Gynecology, Jikei University Daisan Hospital, Izumi-honnchou, Komae-shi, Tokyo. isonishi@jikei.ac.jp
authors.forename: Seiji
authors.initials: S
authors.lastname: Isonishi
authors.forename: Motoaki
authors.initials: M
authors.lastname: Saito
authors.forename: Misato
authors.initials: M
authors.lastname: Saito
authors.forename: Tadao
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D016895:Culture Media, Serum-Free / Q000378:metabolism / Q000494:pharmacology*; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D043823:Taxoids / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016895:Culture Media, Serum-Free; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel