Effect of Modified Alkaline Supplementation on Syngenic Melanoma Growth in CB57/BL Mice

被引:32
作者
Azzarito, Tommaso [1 ]
Lugini, Luana [1 ]
Spugnini, Enrico Pierluigi [2 ]
Canese, Rossella [3 ]
Gugliotta, Alessio [1 ]
Fidanza, Stefano [1 ]
Fais, Stefano [1 ]
机构
[1] Natl Inst Hlth, Dept Drug Res & Med Evaluat, Rome, Italy
[2] Regina Elena Inst Canc Res, SAFU Dept, Rome, Italy
[3] Natl Inst Hlth, Dept Cell Biol & Neurosci, Rome, Italy
来源
PLOS ONE | 2016年 / 11卷 / 07期
关键词
PROTON PUMP INHIBITORS; MICROENVIRONMENT ACIDITY; COMPANION ANIMALS; PHASE I/II; LANSOPRAZOLE; RESISTANCE; CANCER; TUMORS; CARCINOGENESIS; CHEMOTHERAPY;
D O I
10.1371/journal.pone.0159763
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Tumor extracellular acidity is a hallmark of malignant cancers. Thus, in this study we evaluated the effects of the oral administration of a commercially available water alkalizer (Basenpulver (R)) (BP) on tumor growth in a syngenic melanoma mouse model. The alkalizer was administered daily by oral gavage starting one week after tumor implantation in CB57/BL mice. Tumors were calipered and their acidity measured by in vivo MRI guided P-31 MRS. Furthermore, urine pH was monitored for potential metabolic alkalosis. BP administration significantly reduced melanoma growth in mice; the optimal dose in terms of tolerability and efficacy was 8 g/l (p<0.05). The in vivo results were supported by in vitro experiments, wherein BP-treated human and murine melanoma cell cultures exhibited a dose-dependent inhibition of tumor cell growth. This investigation provides the first proof of concept that systemic buffering can improve tumor control by itself and that this approach may represent a new strategy in prevention and/or treatment of cancers.
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页数:13
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共 43 条
  • [1] [Anonymous], J ENZYME INHIB MED C
  • [2] Lansoprazole induces sensitivity to suboptimal doses of paclitaxel in human melanoma
    Azzarito, Tommaso
    Venturi, Giulietta
    Cesolini, Albino
    Fais, Stefano
    [J]. CANCER LETTERS, 2015, 356 (02) : 697 - 703
  • [3] The acidity of the tumor microenvironment is a mechanism of immune escape that can be overcome by proton pump inhibitors
    Bellone, Matteo
    Calcinotto, Arianna
    Filipazzi, Paola
    De Milito, Angelo
    Fais, Stefano
    Rivoltini, Licia
    [J]. ONCOIMMUNOLOGY, 2013, 2 (01):
  • [4] Lifestyle modification for resistant hypertension: The TRIUMPH randomized clinical trial
    Blumenthal, James A.
    Sherwood, Andrew
    Smith, Patrick J.
    Mabe, Stephanie
    Watkins, Lana
    Lin, Pao-Hwa
    Craighead, Linda W.
    Babyak, Michael
    Tyson, Crystal
    Young, Kenlyn
    Ashworth, Megan
    Kraus, William
    Liao, Lawrence
    Hinderliter, Alan
    [J]. AMERICAN HEART JOURNAL, 2015, 170 (05) : 986 - U176
  • [5] Regulation of cancer cell metabolism
    Cairns, Rob A.
    Harris, Isaac S.
    Mak, Tak W.
    [J]. NATURE REVIEWS CANCER, 2011, 11 (02) : 85 - 95
  • [6] Modulation of Microenvironment Acidity Reverses Anergy in Human and Murine Tumor-Infiltrating T Lymphocytes
    Calcinotto, Arianna
    Filipazzi, Paola
    Grioni, Matteo
    Iero, Manuela
    De Milito, Angelo
    Ricupito, Alessia
    Cova, Agata
    Canese, Rossella
    Jachetti, Elena
    Rossetti, Monica
    Huber, Veronica
    Parmiani, Giorgio
    Generoso, Luca
    Santinami, Mario
    Borghi, Martina
    Fais, Stefano
    Bellone, Matteo
    Rivoltini, Licia
    [J]. CANCER RESEARCH, 2012, 72 (11) : 2746 - 2756
  • [7] Reversal Effects of Pantoprazole on Multidrug Resistance in Human Gastric Adenocarcinoma Cells by Down-Regulating the V-ATPases/mTOR/HIF-1α/P-gp and MRP1 Signaling Pathway In Vitro and In Vivo
    Chen, Min
    Huang, Shu-Ling
    Zhang, Xiao-Qi
    Zhang, Bin
    Zhu, Hao
    Yang, Vincent W.
    Zou, Xiao-Ping
    [J]. JOURNAL OF CELLULAR BIOCHEMISTRY, 2012, 113 (07) : 2474 - 2487
  • [8] Effects and mechanisms of proton pump inhibitors as a novel chemosensitizer on human gastric adenocarcinoma (SGC7901) cells
    Chen, Min
    Zou, Xiaoping
    Luo, Hesheng
    Cao, Jun
    Zhang, Xiaoqi
    Zhang, Bin
    Liu, Wenjia
    [J]. CELL BIOLOGY INTERNATIONAL, 2009, 33 (09) : 1008 - 1019
  • [9] De Milito Angelo, 2005, Future Oncol, V1, P779, DOI 10.2217/14796694.1.6.779
  • [10] Proton pump inhibitors induce apoptosis of human B-cell tumors through a caspase-independent mechanism involving reactive oxygen species
    De Milito, Angelo
    Iessi, Elisabetta
    Logozzi, Mariantonia
    Lozupone, Francesco
    Spada, Massimo
    Marino, Maria Lucia
    Federici, Cristina
    Perdicchio, Maurizio
    Matarrese, Paola
    Lugini, Luana
    Nilsson, Anna
    Fais, Stefano
    [J]. CANCER RESEARCH, 2007, 67 (11) : 5408 - 5417