Open Access

Anagliptin promotes apoptosis in mouse colon carcinoma cells via MCT‑4/lactate‑mediated intracellular acidosis

  • Authors:
    • Qi Li
    • Xiaoling Qin
    • Xiaotong Kou
    • Jingyu Li
    • Zhongsha Li
    • Chang Chen
  • View Affiliations

  • Published online on: February 15, 2022     https://doi.org/10.3892/etm.2022.11211
  • Article Number: 282
  • Copyright : © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

Cancer cells frequently exhibit an acidic extracellular microenvironment, where inversion of the transmembrane pH gradient is associated with tumor proliferation and metastasis. To elucidate a new therapeutic target against cancer, the current study aimed to determine the mechanism by which the dipeptidyl peptidase‑4 inhibitor anagliptin regulates the cellular pH gradient and concomitant extracellular acidosis during cancer progression. A total of 5x105 CT‑26 cells (resuspended in phosphate buffer saline) were injected subcutaneously in the right flank of male BALB/c mice (weighing 25‑28 g). The tumor samples were harvested, and lactate was detected using a lactate assay kit. Immunohistochemistry was used to detect the Ki67 and PCNA. MTT assay and flow cytometric were used to detect cell viability. Intracellular pH was detected by fluorescence pH indicator. The results revealed that anagliptin effectively reduced tumor growth, but did not affect the body weight of treated mice. Anagliptin reduced the accumulation of lactate in tumor sample. Treatment with anagliptin stimulated the apoptosis of CT‑26 cells. And lactate excretion inhibition is accompanied by an increase in extracellular pH (pHe) after treatment with anagliptin. Furthermore, anagliptin induced intracellular acidification and reversed the low pHe gradient via monocarboxylate transporter‑4 (MCT‑4)‑mediated lactate excretion. Additionally, anagliptin reversed the aberrant transmembrane extracellular/intracellular pH gradient by suppressing MCT‑4‑mediated lactate excretion, while also reducing mitochondrial membrane potential and inducing apoptosis. These data revealed a novel function of anagliptin in regulating lactate excretion from cancer cells, suggesting that anagliptin may be used as a potential treatment for cancer.
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April-2022
Volume 23 Issue 4

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Li Q, Qin X, Kou X, Li J, Li Z and Chen C: Anagliptin promotes apoptosis in mouse colon carcinoma cells via MCT‑4/lactate‑mediated intracellular acidosis. Exp Ther Med 23: 282, 2022
APA
Li, Q., Qin, X., Kou, X., Li, J., Li, Z., & Chen, C. (2022). Anagliptin promotes apoptosis in mouse colon carcinoma cells via MCT‑4/lactate‑mediated intracellular acidosis. Experimental and Therapeutic Medicine, 23, 282. https://doi.org/10.3892/etm.2022.11211
MLA
Li, Q., Qin, X., Kou, X., Li, J., Li, Z., Chen, C."Anagliptin promotes apoptosis in mouse colon carcinoma cells via MCT‑4/lactate‑mediated intracellular acidosis". Experimental and Therapeutic Medicine 23.4 (2022): 282.
Chicago
Li, Q., Qin, X., Kou, X., Li, J., Li, Z., Chen, C."Anagliptin promotes apoptosis in mouse colon carcinoma cells via MCT‑4/lactate‑mediated intracellular acidosis". Experimental and Therapeutic Medicine 23, no. 4 (2022): 282. https://doi.org/10.3892/etm.2022.11211