pH gradient reversal

An emerging hallmark of cancers

Mohit Sharma, Madhusudan Astekar, Sonal Soi, Bhari S. Manjunatha, Devi C. Shetty, Raghu Radhakrishnan

Research output: Contribution to journalReview article

17 Citations (Scopus)

Abstract

Several tumors exhibit pH gradient reversal, with acidification of extracellular pH (pHe) and alkalinization of intracellular pH (pHi). The pH gradient reversal is evident even during the preliminary stages of tumorigenesis and is crucial for survival and propagation of tumors, irrespective of their pathology, genetics and origins. Moreover, this hallmark seems to be present ubiquitously in all malignant tumors. Based on these facts, we propose a new emerging hallmark of cancer “pH gradient reversal”. Normalizing pH gradient reversal through inhibition of various proton transporters such as Na+-H+ exchanger (NHE), Vacuolar-type H+-ATPase (V-ATPase), H+/K+-ATPases and carbonic anhydrases (CAs) has demonstrated substantial therapeutic benefits. Indeed, inhibition of NHE1 is now being regarded as the latest concept in cancer treatment. A recent patent deals with the utilization of cis-Urocanic acid to acidify the pHi and induce apoptosis in tumors. Another patent reports therapeutic benefit by inhibiting Lactate Dehydrogenase - 5 (LDH-5) in various cancers. Several patents have been formulated by designing drugs activated through acidic pHe providing a cancer specific action. The purpose of this review is to analyze the available literature and help design selective therapies that could be a valuable adjunct to the conventional therapies or even replace them.

Original languageEnglish
Pages (from-to)244-258
Number of pages15
JournalRecent Patents on Anti-Cancer Drug Discovery
Volume10
Issue number3
Publication statusPublished - 01-10-2015

Fingerprint

Proton-Motive Force
Neoplasms
NSC 153174
Urocanic Acid
Vacuolar Proton-Translocating ATPases
Sodium-Hydrogen Antiporter
Proton-Translocating ATPases
Carbonic Anhydrases
Patents
Therapeutics
Protons
Carcinogenesis
Apoptosis
Pathology

All Science Journal Classification (ASJC) codes

  • Oncology
  • Drug Discovery
  • Cancer Research
  • Pharmacology (medical)

Cite this

Sharma, M., Astekar, M., Soi, S., Manjunatha, B. S., Shetty, D. C., & Radhakrishnan, R. (2015). pH gradient reversal: An emerging hallmark of cancers. Recent Patents on Anti-Cancer Drug Discovery, 10(3), 244-258.
Sharma, Mohit ; Astekar, Madhusudan ; Soi, Sonal ; Manjunatha, Bhari S. ; Shetty, Devi C. ; Radhakrishnan, Raghu. / pH gradient reversal : An emerging hallmark of cancers. In: Recent Patents on Anti-Cancer Drug Discovery. 2015 ; Vol. 10, No. 3. pp. 244-258.
@article{5fee78ea25ac4e3fa73cfe4578707c9f,
title = "pH gradient reversal: An emerging hallmark of cancers",
abstract = "Several tumors exhibit pH gradient reversal, with acidification of extracellular pH (pHe) and alkalinization of intracellular pH (pHi). The pH gradient reversal is evident even during the preliminary stages of tumorigenesis and is crucial for survival and propagation of tumors, irrespective of their pathology, genetics and origins. Moreover, this hallmark seems to be present ubiquitously in all malignant tumors. Based on these facts, we propose a new emerging hallmark of cancer “pH gradient reversal”. Normalizing pH gradient reversal through inhibition of various proton transporters such as Na+-H+ exchanger (NHE), Vacuolar-type H+-ATPase (V-ATPase), H+/K+-ATPases and carbonic anhydrases (CAs) has demonstrated substantial therapeutic benefits. Indeed, inhibition of NHE1 is now being regarded as the latest concept in cancer treatment. A recent patent deals with the utilization of cis-Urocanic acid to acidify the pHi and induce apoptosis in tumors. Another patent reports therapeutic benefit by inhibiting Lactate Dehydrogenase - 5 (LDH-5) in various cancers. Several patents have been formulated by designing drugs activated through acidic pHe providing a cancer specific action. The purpose of this review is to analyze the available literature and help design selective therapies that could be a valuable adjunct to the conventional therapies or even replace them.",
author = "Mohit Sharma and Madhusudan Astekar and Sonal Soi and Manjunatha, {Bhari S.} and Shetty, {Devi C.} and Raghu Radhakrishnan",
year = "2015",
month = "10",
day = "1",
language = "English",
volume = "10",
pages = "244--258",
journal = "Recent Patents on Anti-Cancer Drug Discovery",
issn = "1574-8928",
publisher = "Bentham Science Publishers B.V.",
number = "3",

}

Sharma, M, Astekar, M, Soi, S, Manjunatha, BS, Shetty, DC & Radhakrishnan, R 2015, 'pH gradient reversal: An emerging hallmark of cancers', Recent Patents on Anti-Cancer Drug Discovery, vol. 10, no. 3, pp. 244-258.

pH gradient reversal : An emerging hallmark of cancers. / Sharma, Mohit; Astekar, Madhusudan; Soi, Sonal; Manjunatha, Bhari S.; Shetty, Devi C.; Radhakrishnan, Raghu.

In: Recent Patents on Anti-Cancer Drug Discovery, Vol. 10, No. 3, 01.10.2015, p. 244-258.

Research output: Contribution to journalReview article

TY - JOUR

T1 - pH gradient reversal

T2 - An emerging hallmark of cancers

AU - Sharma, Mohit

AU - Astekar, Madhusudan

AU - Soi, Sonal

AU - Manjunatha, Bhari S.

AU - Shetty, Devi C.

AU - Radhakrishnan, Raghu

PY - 2015/10/1

Y1 - 2015/10/1

N2 - Several tumors exhibit pH gradient reversal, with acidification of extracellular pH (pHe) and alkalinization of intracellular pH (pHi). The pH gradient reversal is evident even during the preliminary stages of tumorigenesis and is crucial for survival and propagation of tumors, irrespective of their pathology, genetics and origins. Moreover, this hallmark seems to be present ubiquitously in all malignant tumors. Based on these facts, we propose a new emerging hallmark of cancer “pH gradient reversal”. Normalizing pH gradient reversal through inhibition of various proton transporters such as Na+-H+ exchanger (NHE), Vacuolar-type H+-ATPase (V-ATPase), H+/K+-ATPases and carbonic anhydrases (CAs) has demonstrated substantial therapeutic benefits. Indeed, inhibition of NHE1 is now being regarded as the latest concept in cancer treatment. A recent patent deals with the utilization of cis-Urocanic acid to acidify the pHi and induce apoptosis in tumors. Another patent reports therapeutic benefit by inhibiting Lactate Dehydrogenase - 5 (LDH-5) in various cancers. Several patents have been formulated by designing drugs activated through acidic pHe providing a cancer specific action. The purpose of this review is to analyze the available literature and help design selective therapies that could be a valuable adjunct to the conventional therapies or even replace them.

AB - Several tumors exhibit pH gradient reversal, with acidification of extracellular pH (pHe) and alkalinization of intracellular pH (pHi). The pH gradient reversal is evident even during the preliminary stages of tumorigenesis and is crucial for survival and propagation of tumors, irrespective of their pathology, genetics and origins. Moreover, this hallmark seems to be present ubiquitously in all malignant tumors. Based on these facts, we propose a new emerging hallmark of cancer “pH gradient reversal”. Normalizing pH gradient reversal through inhibition of various proton transporters such as Na+-H+ exchanger (NHE), Vacuolar-type H+-ATPase (V-ATPase), H+/K+-ATPases and carbonic anhydrases (CAs) has demonstrated substantial therapeutic benefits. Indeed, inhibition of NHE1 is now being regarded as the latest concept in cancer treatment. A recent patent deals with the utilization of cis-Urocanic acid to acidify the pHi and induce apoptosis in tumors. Another patent reports therapeutic benefit by inhibiting Lactate Dehydrogenase - 5 (LDH-5) in various cancers. Several patents have been formulated by designing drugs activated through acidic pHe providing a cancer specific action. The purpose of this review is to analyze the available literature and help design selective therapies that could be a valuable adjunct to the conventional therapies or even replace them.

UR - http://www.scopus.com/inward/record.url?scp=84947760937&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84947760937&partnerID=8YFLogxK

M3 - Review article

VL - 10

SP - 244

EP - 258

JO - Recent Patents on Anti-Cancer Drug Discovery

JF - Recent Patents on Anti-Cancer Drug Discovery

SN - 1574-8928

IS - 3

ER -

Sharma M, Astekar M, Soi S, Manjunatha BS, Shetty DC, Radhakrishnan R. pH gradient reversal: An emerging hallmark of cancers. Recent Patents on Anti-Cancer Drug Discovery. 2015 Oct 1;10(3):244-258.