title: Curcumin hampers the antitumor effect of vinblastine via the inhibition of microtubule dynamics and mitochondrial membrane potential in HeLa cervical cancer cells.
abstract: BACKGROUND
  Curcumin, a major component of curry powder, which is a natural polyphenol product extracted from rhizoma curcumae longae, interacts with a specific binding site on microtubules. Vinblastine is an antitumor drug that induces microtubule depolymerization.
  
  
  OBJECTIVE
  We investigated whether curcumin influences the antitumor effect of vinblastine in HeLa human cervical cancer cells.
  
  
  METHODS
  Changes in microtubule filaments were visualized by immuno-staining. Cell death was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) or water-soluble tetrazolium(WST) assay. Apoptotic cell formation was assessed by flow cytometry after staining cells with propidium iodide(PI) and/or Annexin V or with 6-diamidino-2-phenylindole(DAPI). Reactive oxygen species(ROS) were also measured by flow cytometry using dichloro-dihydro-fluorescein diacetate(DCF-DA). JC-1 was used to determine mitochondrial membrane potential (MMP).
  
  
  RESULTS
  When cells were pretreated with curcumin, microtubule filaments were disordered. Vinblastine-induced microtubule depolymerization and cell death were reduced in HeLa human cervical cancer cells pretreated with curcumin compared to the control. The decrease in cell death was much greater in cells pretreated with curcumin compared to cotreatment or post-treatment. DNA condensation by vinblastine was also decreased in curcumin-pretreated cells. Curcumin reduced ROS production by vinblastine. However, no changes in vinblastine-mediated microtubule depolymerization were detected upon N-acetylcysteine(NAC) treatment. In contrast, vinblastine-induced MMP collapse was inhibited by pretreatment with curcumin or NAC. These findings suggest that vinblastine-induced tumor cell death might be inhibited by curcumin via ROS-independent microtubule dynamics and ROS-dependent MMP collapse. It also suggests that microtubule dynamics could be necessary for the optimal antitumor activity of vinblastine. Our results suggest that patients treated with vinblastine should not consume curcumin.
authors.affiliation: Department of Bioscience and Biotechnology, Sejong University, Seoul 05006, Republic of Korea.
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Bioscience and Biotechnology, Sejong University, Seoul 05006, Republic of Korea.
authors.forename: Sojin
authors.initials: S
authors.lastname: Park
authors.affiliation: College of Pharmacy, Gachon University, #191 Hambakmoero, Yeonsu-gu, Incheon 406-799, Republic of Kore.
authors.forename: Sun Yeou
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Kyunggi-do 16419, Republic of Korea. Electronic address: shum@skku.edu.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Um
authors.affiliation: Department of Bioscience and Biotechnology, Sejong University, Seoul 05006, Republic of Korea. Electronic address: eunyimoon@sejong.ac.kr.
authors.forename: Eun-Yi
authors.initials: EY
authors.lastname: Moon
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D014747:Vinblastine / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D014747:Vinblastine; C505409:Casp3 protein, mouse; D053148:Caspase 3; C022616:thiazolyl blue; D003474:Curcumin
keywords: Curcumin; Microtubule; Mitochondrial membrane potential; ROS, Antitumor activity; Vinblastine