title: Hesperidin as a preventive resistance agent in MCF-7 breast cancer cells line resistance to doxorubicin.
abstract: OBJECTIVE
  To evaluate of hesperidin to overcome resistance of doxorubicin in MCF-7 resistant doxorubicin cells (MCF-7/Dox) in cytotoxicity apoptosis and P-glycoprotein (Pgp) expression in combination with doxorubicin.
  
  
  METHODS
  The cytotoxic properties, 50% inhibition concentration (IC50) and its combination with doxorubicin in MCF-7 cell lines resistant to doxorubicin (MCF-7/Dox) cells were determined using MTT assay. Apoptosis induction was examined by double staining assay using ethidium bromide-acridine orange. Immunocytochemistry assay was performed to determine the level and localization of Pgp.
  
  
  RESULTS
  Single treatment of hesperidin showed cytotoxic activity on MCF-7/Dox cells with IC50 value of 11 µmol/L. Thus, combination treatment from hesperidin and doxorubicin showed addictive and antagonist effect (CI>1.0). Hesperidin did not increase the apoptotic induction, but decreased the Pgp expressions level when combined with doxorubicin in low concentration.
  
  
  CONCLUSIONS
  Hesperidin has cytotoxic effect on MCF-7/Dox cells with IC50 of 11 µmol/L. Hesperidin did not increased the apoptotic induction combined with doxorubicin. Co-chemotherapy application of doxorubicin and hesperidin on MCF-7/Dox cells showed synergism effect through inhibition of Pgp expression.
authors.affiliation: Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Yogyakarta, Indonesia ; Pharmacy study programme, Faculty of Medicine and Health Sciences, Universitas Muhammadiyah Yogyakarta, Yogyakarta, Indonesia.
authors.forename: Rifki
authors.initials: R
authors.lastname: Febriansah
authors.affiliation: Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Yogyakarta, Indonesia.
authors.forename: Dyaningtyas Dewi Pamungkas
authors.initials: DD
authors.lastname: Putri
authors.affiliation: Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Yogyakarta, Indonesia ; Faculty of Pharmacy, Universitas Jenderal Soedirman, Purwokerto, Indonesia.
authors.lastname: Sarmoko
authors.affiliation: Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Yogyakarta, Indonesia ; Faculty of Pharmacy, Universitas Muhammadiyah Purwokerto, Purwokerto, Indonesia.
authors.forename: Nunuk Aries
authors.initials: NA
authors.lastname: Nurulita
authors.affiliation: Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Yogyakarta, Indonesia.
authors.forename: Edy
authors.initials: E
authors.lastname: Meiyanto
authors.affiliation: Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Yogyakarta, Indonesia.
authors.forename: Agung Endro
authors.initials: AE
authors.lastname: Nugroho
keywords: Apoptosis; Doxorubicin; Hesperidin; MCF-7/Dox cells line; Pgp expression