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Dykes SS, Friday E, Pruitt K, et al. The histone deacetylase inhibitor cambinol prevents acidic pH. Biochem Biophys Rep. 2015;3:83-93doi: 10.1016/j.bbrep.2015.07.015.
Dykes, S. S., Friday, E., Pruitt, K., & Cardelli, J. A. (2015). The histone deacetylase inhibitor cambinol prevents acidic pH. Biochemistry and biophysics reports, 383-93. https://doi.org/10.1016/j.bbrep.2015.07.015
Dykes, Samantha S, et al. "The histone deacetylase inhibitor cambinol prevents acidic pH." Biochemistry and biophysics reports vol. 3 (2015): 83-93. doi: https://doi.org/10.1016/j.bbrep.2015.07.015
Dykes SS, Friday E, Pruitt K, Cardelli JA. The histone deacetylase inhibitor cambinol prevents acidic pH. Biochem Biophys Rep. 2015 Jul 26;3:83-93. doi: 10.1016/j.bbrep.2015.07.015. eCollection 2015 Sep. PMID: 29124170; PMCID: PMC5668693.
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Biochem Biophys Rep. 2015 Jul 26;3:83-93. doi: 10.1016/j.bbrep.2015.07.015. eCollection 2015 Sep.

The histone deacetylase inhibitor cambinol prevents acidic pH.

Biochemistry and biophysics reports

Samantha S Dykes, Ellen Friday, Kevin Pruitt, James A Cardelli

Affiliations

  1. Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, United States.
  2. Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, United States.
  3. Department of Medicine, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 7113, United States.
  4. Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, United States.

PMID: 29124170 PMCID: PMC5668693 DOI: 10.1016/j.bbrep.2015.07.015

Abstract

Common features of the solid tumor microenvironment, such as acidic extracellular pH and growth factors, are known to induce the redistribution of lysosomes from a perinuclear region to a position near the plasma membrane. Lysosome/plasma membrane juxtaposition facilitates invasion by allowing for the release of lysosomal proteases, including cathepsin B, which contribute to matrix degradation. In this study we identified the sirtuin 1/sirtuin 2 (SIRT1/2) inhibitor cambinol acts as a drug that inhibits lysosome redistribution and tumor invasion. Treatment of cells with cambinol resulted in a juxtanuclear lysosome aggregation (JLA) similar to that seen upon treatment with the PPARĪ³ agonist, troglitazone (Tro). Like Tro, cambinol required the activity of ERK1/2 in order to induce this lysosome clustering phenotype. However, cambinol did not require the activity of Rab7, suggesting that this drug causes JLA by a mechanism different from what is known for Tro. Additionally, cambinol-induced JLA was not a result of autophagy induction. Further investigation revealed that cambinol triggered JLA independently of its activity as a SIRT1/2 inhibitor, suggesting that this drug could have effects in addition to SIRT1/2 inhibition that could be developed into a novel anti-cancer therapy.

Keywords: Acidic pHe; Cambinol; EIPA, ethyl-isopropyl amiloride; ERK; HDAC, histone deacetylase; JLA, juxtanuclear lysosome aggregation; LAMP-1, lysosome associated membrane protein 1; Lysosome trafficking; MTOC, microtubule organizing center; NHE, sodium proton exchanger; Rab7; SIRT, sirtuin; Tro, troglitazone; Troglitazone; pHe, extracellular pH

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