title: Highly Halaven-resistant KBV20C Cancer Cells Can Be Sensitized by Co-treatment with Fluphenazine.
abstract: To identify conditions that induce an increase in the sensitivity of highly Halaven (HAL)-resistant cancer cells compared to sensitive cells.
  
  
  
  We observed that drug-resistant KBV20C cells are highly resistant to HAL compared to other antimitotic drugs. The concentration required to treat KBV20C cells was almost 500-fold higher than that used to treat sensitive parent KB cells. In order to increase sensitization, HAL-treated KBV20C cells were co-treated with the repositioned drug, fluphenazine (FLU).
  
  
  
  HAL and FLU co-treatment inhibited the growth and increased apoptosis via G2arrest in HAL-treated KBV20C cancer cells. Sensitization by HAL-FLU affected retinoblastoma protein (pRB), pHistone H3 and pH2AX protein levels. FLU could also inhibit p-glycoprotein (P-gp) activity in HA-resistant KBV20C cells. These observations suggest that the mechanisms underlying FLU-HAL sensitization in resistant KBV20C cells involve both apoptosis and P-gp inhibition. Furthermore, both thioridazine (THIO) and mefloquine (MEF), but not azathioprine (AZA), sensitized HAL-treated KBV20C cells.
  
  
  
  These findings provide important information regarding the sensitization of HAL-resistant cells and indicate that FLU, THIO and MEF may have similar sensitization effects in highly HAL-resistant cells.
authors: School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
authors: Ji Hyun
authors: JH
authors: Cheon
authors: School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
authors: Byung Mu
authors: BM
authors: Lee
authors: School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea hkims@skku.edu syoon88@gmail.com.
authors: Hyung Sik
authors: HS
authors: Kim
authors: School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea hkims@skku.edu syoon88@gmail.com.
authors: Sungpil
authors: S
authors: Yoon
mesh_terms: D045744:Cell Line, Tumor; D005476:Fluphenazine / Q000494:pharmacology*; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D007659:Ketones / Q000494:pharmacology*; D000095662:Polyether Polyketides
chemical_list: D005476:Fluphenazine; D005663:Furans; D007659:Ketones; C490954:eribulin; D000095662:Polyether Polyketides
keywords: Halaven; P-gp; drug-resistance; fluphenazine; mefloquine; thioridazine