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Combination of lactate calcium salt with 5-indanesulfonamide and -cyano-4-hydroxycinnamic acid to enhance the antitumor effect on HCT116 cells via intracellular acidification

Authors
Jeong, Keun-YeongMander, PoonamSim, Jae JunKim, Hwan Mook
Issue Date
Mar-2016
Publisher
SPANDIDOS PUBL LTD
Keywords
colon cancer; lactate calcium salt; carbonic anhydrase 9; monocarboxylate transporter 4; cellular pH; antitumor effect
Citation
ONCOLOGY LETTERS, v.11, no.3, pp.1866 - 1872
Journal Title
ONCOLOGY LETTERS
Volume
11
Number
3
Start Page
1866
End Page
1872
URI
https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/8507
DOI
10.3892/ol.2016.4137
ISSN
1792-1074
Abstract
Maintenance of a neutral intracellular pH (pHi) is favorable for the survival of tumors, and maintenance of highly acidic extracellular pH (pHe) facilitates tumor invasiveness. The aim of the present study was to investigate the antitumor effects of lactate calcium salt (CaLa), 5-indanesulfonamide (IS) and -cyano-4-hydroxycinnamic acid (CA) via pH regulation in colon cancer cells. HCT116 cells were treated with CaLa, IS, CA and combinations of the three. Subsequently, the concentration of intracellular lactate was determined. pHi and pHe were measured using cell lysates and culture media. Colony formation assay, cell viability assay and western blot analysis were additionally performed to analyze the consequences of the pH changes. CaLa, IS, CA and combination treatments induced an increase in the concentration of intracellular lactate. Lactate influx into the tumor microenvironment produced an acidic pHi in colon cancer cells. Consequently, colony formation and cell viability were significantly decreased, as well as poly(adenosine diphosphate-ribose) polymerase degradation. The tumor microenvironment may be exploited therapeutically by disrupting the mechanism that regulates pHi, leading to cell apoptosis. The present study indicated that treatment with CaLa, IS and CA induced intracellular acidification via lactate influx, causing apoptosis of colon cancer cells. Additionally, the findings suggested that the combination of CaLa with IS and CA may enhance antitumor activity, and may provide a potential therapeutic approach for the treatment of colon cancer.
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