Journal of
Medicinal Plants Research

  • Abbreviation: J. Med. Plants Res.
  • Language: English
  • ISSN: 1996-0875
  • DOI: 10.5897/JMPR
  • Start Year: 2007
  • Published Articles: 3793

Full Length Research Paper

Reversal effect of nimodipine on cytarabine-resistant HL60 cells associated with triggering apoptosis

Ling-zhen Wang1, Ling-li Wang2, Xiao-ling Li1, Li-rong Sun3*, Zhi Wang4 and Liang Song5
1Department of Pediatric Hematology,The Affiliated Hospital of Medical College, Qingdao University, NO.16, Jiangsu Road, Shandong 266003, P. R. China. 2Department of Stomatology, Weihai municipal hospital, No.70, Heping Road, Shandong 264200, P. R. China. 3Department of Pediatric Hematology, the Affiliated Hospital of Medical College, Qingdao University, No.16, Jiangsu Road, Shandong 266003, P. R. China. 4Department of Pharmacy, the Affiliated Hospital of Medical College, Qingdao University, No.16, Jiangsu Road, Shandong 266003, P. R. China. 5Second department of internal medicine, Qingdao Children’s hospital, No.27, Wuding Road, Shandong, 266003, P. R. China.
Email: [email protected]

  •  Accepted: 11 July 2013
  •  Published: 25 July 2013

Abstract

Intrinsic or acquired drug resistance is the major reason for failure of cancer therapy. Multifactorial mechanisms are involved in multidrug resistance (MDR). Various arrays of drugs are indentified that sensitize multidrug–resistant cells to chemotherapy. The present study aimed to study whether nimodipine (NMDP) could reverse MDR and what mechanism is involved in the reversal effect. Cytarabine (Ara-c)-resistant HL60 leukemia cells (HL60/Ara-c) were treated with free Ara-c, free NMDP or combination of Ara-c with NMDP. The apoptotic effects were enhanced with increase of concentration, showing a dose-dependent manner. Combination of Ara-c with NMDP arrest more cells in G0/G1 phase. Bcl-2 mRNA and protein expression significantly decreased in co-administration group, while that of Bax increased. The activity of caspase-3 was remarkably activated by combination of Ara-c with NMDP, which was correlated with modulating Bcl-2/Bax. Intracellular Ca2+ concentration was significantly increased over culture time in co-administration group. In the xenograft model, antitumor activity of NMDP with Ara-c was signifanctly enhanced. In conclusion, the reversal effect of NMDP on HL60/Ara-c cells is associated with modulating proapoptotic and antiapoptotic protein expression changes and initiating a cascade of caspase activation. Combination of anticancer agents with a modulator may provide a novel strategy for improving the chemotherapeutic effects.

 

Key words:  Nimodipine, cytarabine, multidrug resistance, leukemia.