Anticancer Effects of Valproic Acid on Esophageal Stem-like Carcinoma Cells

被引:0
作者
Saboor-Maleki, Saffiyeh [1 ]
Rassouli, Fatemeh B. [1 ,2 ]
Matin, Maryam M. [1 ,2 ]
Mousavi, Mandi [1 ]
机构
[1] Ferdowsi Univ Mashhad, Dept Biol, Fac Sci, Mashhad, Iran
[2] Ferdowsi Univ Mashhad, Inst Biotechnol, Cell & Mol Biotechnol Res Grp, Mashhad, Iran
关键词
valproic acid; esophageal squamous cell carcinoma; synergic activity; HISTONE DEACETYLASE INHIBITOR; NECK-CANCER; DIFFERENTIATION; GROWTH; COMBINATION; INDUCTION; HEAD;
D O I
10.16476/j.pibb.2016.0053
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Valproic acid (VPA) is a histone deacetylase inhibitor that has been an object of interest to clinicians for its promising potency in cancer therapy, as it induces apoptosis and differentiation, and enhances of chemotherapy sensitivity. Esophageal squamous cell carcinoma (ESCC) is a malignant disease with growing incidence and low survival rate. Due to limited information on VPA activity in ESCC cells, we aimed to determine effects of VPA on chemotherapy responsiveness and expression of malignant markers in ESCC stem-like cells. Upon coadministration of non-toxic VPA + cisplatin (DDP), paclitaxel and 5-fluorouracil, viability of KYSE30 cells was assessed, and induced apoptosis was evaluated by DAPI staining, DNA laddering and flow cytometry. In addition, real time RT-PCR was performed to study changes in the expression of P21, CD44 and BMI-1 upon treatments. MTT test demonstrated that VPA significantly (P < 0.05) increased toxicity of DDP, which was confirmed by DNA laddering, flow cytometry analysis and significant (P < 0.05) overexpression of P21. Moreover, real time RT-PCR results indicated significant (P < 0.05) down regulation of CD44 and BMI-1 after VPA administration. Present attempt provided evidence, for the first time, that VPA not only improved responsiveness of esophageal stem-like cancer cells to DDP, also negatively regulated cancer stem cells markers in these cells.
引用
收藏
页码:903 / 909
页数:7
相关论文
共 30 条
[1]   Valproic acid, an anti-epileptic drug and a histone deacetylase inhibitor, in combination with proteasome inhibitors exerts antiproliferative, pro-apoptotic and chemosensitizing effects in human colorectal cancer cells: Underlying molecular mechanisms [J].
Abaza, Mohamed-Salah I. ;
Bahman, Abdul-Majeed ;
Al-Attiyah, Raja'a J. .
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2014, 34 (02) :513-532
[2]   The Effects of Histone Deacetylase Inhibitors on Glioblastoma-Derived Stem Cells [J].
Alvarez, Angel A. ;
Field, Melvin ;
Bushnev, Sergey ;
Longo, Matthew S. ;
Sugaya, Kiminobu .
JOURNAL OF MOLECULAR NEUROSCIENCE, 2015, 55 (01) :7-20
[3]  
[Anonymous], TECHNOL CANC RES TRE
[4]  
[Anonymous], TECHNOL CANC RES TRE
[5]   The sequence of application of methotrexate and histone deacetylase inhibitors determines either a synergistic or an antagonistic response in childhood acute lymphoblastic leukemia cells [J].
Bastian, L. ;
Einsiedel, H. G. ;
Henze, G. ;
Seeger, K. ;
Shalapour, S. .
LEUKEMIA, 2011, 25 (02) :359-361
[6]   Postradiation sensitization of the histone deacetylase inhibitor valproic acid [J].
Chinnaiyan, Prakash ;
Cerna, David ;
Burgan, William E. ;
Beam, Katie ;
Williams, Eli S. ;
Camphausen, Kevin ;
Tofilon, Philip J. .
CLINICAL CANCER RESEARCH, 2008, 14 (17) :5410-5415
[7]   Valproic acid promotes radiosensitization in meningioma stemlike cells [J].
Chiou, Hsin-Ying Clair ;
Lai, Wen-Kuo ;
Huang, Li-Chun ;
Huang, Shih-Ming ;
Chueh, Sheau-Huei ;
Ma, Hsin-I ;
Hueng, Dueng-Yuan .
ONCOTARGET, 2015, 6 (12) :9959-9969
[8]   Valproic Acid Induced Differentiation and Potentiated Efficacy of Taxol and Nanotaxol for Controlling Growth of Human Glioblastoma LN18 and T98G Cells [J].
Choudhury, Subhasree Roy ;
Karmakar, Surajit ;
Banik, Naren L. ;
Ray, Swapan K. .
NEUROCHEMICAL RESEARCH, 2011, 36 (12) :2292-2305
[9]   New perspectives of valproic acid in clinical practice [J].
Cincarova, Lenka ;
Zdrahal, Zbynek ;
Fajkus, Jiri .
EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2013, 22 (12) :1535-1547
[10]   Valproic acid: Growth inhibition of head and neck cancer by induction of terminal differentiation and senescence [J].
Gan, Chai Phei ;
Hamid, Sharifah ;
Hor, Seen Yii ;
Zain, Rosnah Binti ;
Ismail, Siti Mazlipah ;
Mustafa, Wan Mahadzir Wan ;
Teo, Soo Hwang ;
Saunders, Nicholas ;
Cheong, Sok Ching .
HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, 2012, 34 (03) :344-353