“ The new pH-centric anticancer paradigm in Oncology and Medicine ” ; SCB, 2017

Harguindey, Salvador; Reshkin, Stephan J.

doi:10.1016/j.semcancer.2017.02.008

Cited by 26 publications

(28 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This new and wide-ranging perspective is able to absorb within itself most areas of cancer research. As a consequence of the selective acid–base homeostatic disruption and energetic failure of cellular hydrogen ion (H + ) dynamics, attempts to induce significant intracellular acidification using proton transport and pump inhibitors (PTI and PPI), as well as other intracellular acidifiers and cancer proton reversal (CPR) agents of different origins and natures (repurposed drugs), are becoming an increasingly popular integral therapeutic strategy in cancer treatment [ 4 , 9 ]. The present contribution, from basic to translational to clinically oriented, for the first time, advances an integrated therapeutic approach describing the concerted and progressive utilization of a series of proton-related anti-cancer drugs that can already be used in bedside oncology in the treatment of BC.…”

Section: Introductionmentioning

confidence: 99%

Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New H+-Centered Anticancer Paradigm of the Late Post-Warburg Era

Harguindey¹,

Alfarouk

Orozco³

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

A brand new approach to the understanding of breast cancer (BC) is urgently needed. In this contribution, the etiology, pathogenesis, and treatment of this disease is approached from the new pH-centric anticancer paradigm. Only this unitarian perspective, based upon the hydrogen ion (H+) dynamics of cancer, allows for the understanding and integration of the many dualisms, confusions, and paradoxes of the disease. The new H+-related, wide-ranging model can embrace, from a unique perspective, the many aspects of the disease and, at the same time, therapeutically interfere with most, if not all, of the hallmarks of cancer known to date. The pH-related armamentarium available for the treatment of BC reviewed here may be beneficial for all types and stages of the disease. In this vein, we have attempted a megasynthesis of traditional and new knowledge in the different areas of breast cancer research and treatment based upon the wide-ranging approach afforded by the hydrogen ion dynamics of cancer. The concerted utilization of the pH-related drugs that are available nowadays for the treatment of breast cancer is advanced.

show abstract

Section: Introductionmentioning

confidence: 99%

Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New H+-Centered Anticancer Paradigm of the Late Post-Warburg Era

Harguindey¹,

Alfarouk

Orozco³

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…NHE1 activity or silencing RNA to significantly reduce NHE1 mRNA expression, we demonstrated that NHE1 activation, as evidenced by the intracellular alkalinization, played a key role in the apoptosis induced by B[a]P in F258 cells; this was actually in contrast to the largely described role for NHE1 activation in survival processes [5,9,10], and might be explained by the various functions of the transporter (pH regulator, scaffold protein for signalplex, anchor protein for cytoskeleton) [8], as proposed in section 3-2-1. This non-genotoxic pathway is activated in parallel to the classical p53 pathway (i.e.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 64%

Disturbances in H+ dynamics during environmental carcinogenesis

et al. 2019

View full text Add to dashboard Cite

Abbreviations: B[a]P: benzo[a]pyrene; GPCR: G-protein coupled receptor; MCT: monocarboxylate transporter; NHE1: Na + /H + exchanger 1HIGHLIGHTS Benzo[a]pyrene, a well-known environmental carcinogen, alters H + dynamics. NHE1 activation by B[a]P plays a key role in H + dynamics alterations. B[a]P-altered pH controls cell death/survival balance via mitochondria and lysosome. ABSTRACTDespite the improvement of diagnostic methods and anticancer therapeutics, the human population is still facing an increasing incidence of several types of cancers. According to the World Health Organization, this growing trend would be partly linked to our environment, with around 20% of cancers stemming from exposure to environmental contaminants, notably chemicals like polycyclic aromatic hydrocarbons (PAHs). PAHs are widespread pollutants in our environment resulting from incomplete combustion or pyrolysis of organic material, and thus produced by both natural and anthropic sources; notably benzo[a]pyrene (B[a]P), i.e. the prototypical molecule of this family, that can be detected in cigarette smoke, diesel exhaust particles, occupational-related fumes, and grilled food. This molecule is a well-recognized carcinogen belonging to group 1 carcinogens. Indeed, it can target the different steps of the carcinogenic process and all cancer hallmarks. Interestingly, H + dynamics have been described as key parameters for the occurrence of several, if not all, of these hallmarks. However, information regarding the role of such parameters during environmental carcinogenesis is still very scarce. The present review will thus mainly give an overview of the impact of B[a]P on H + dynamics in liver cells, and will show how such alterations might impact different aspects related to the finely-tuned balance between cell death and survival processes, thereby likely favoring environmental carcinogenesis. In total, the main objective of this review is to encourage further research in this poorly explored field of environmental molecular toxicology.

show abstract

“…The pH dysregulation observed in cancer cells helps to drive tumor processes, which are highly sensitive to even minimum pHi variations: these are cancer initiation, progression, adaptation, proliferation, migration, and the programming and reprogramming of tumor cell metabolism [14,[123][124][125][126][127]. Furthermore, many effects on biologic processes of a cell are generated as a result of pH-sensitive functions such as the regulation of protein expression, the affinity of proteins to bind with a ligand as well as the activity of ion channels/enzymes [124,128]. Some of these pH-sensitive ion channels, enzymes [124,129,130], and processes are described below.…”

Section: Electrolytes-ph Dynamics Interactionsmentioning

confidence: 99%

“…Voltage-gated sodium channels (NaV) Tetrodotoxin (TTX) Sodium-calcium exchanger (Na + /Ca Compound 9t [1,116,123,128,151,152] Na + /K + -ATPase (sodium -potassium adenosine triphosphatase; the Na + /K + pump or sodium-potassium pump)…”

Section: The Name Of Proteins Modulatorsmentioning

confidence: 99%

The Interplay of Dysregulated pH and Electrolyte Imbalance in Cancer

Alfarouk¹,

Ahmed

et al. 2020

Cancers

Self Cite

View full text Add to dashboard Cite

Cancer cells and tissues have an aberrant regulation of hydrogen ion dynamics driven by a combination of poor vascular perfusion, regional hypoxia, and increased the flux of carbons through fermentative glycolysis. This leads to extracellular acidosis and intracellular alkalinization. Dysregulated pH dynamics influence cancer cell biology, from cell transformation and tumorigenesis to proliferation, local growth, invasion, and metastasis. Moreover, this dysregulated intracellular pH (pHi) drives a metabolic shift to increased aerobic glycolysis and reduced mitochondrial oxidative phosphorylation, referred to as the Warburg effect, or Warburg metabolism, which is a selective feature of cancer. This metabolic reprogramming confers a thermodynamic advantage on cancer cells and tissues by protecting them against oxidative stress, enhancing their resistance to hypoxia, and allowing a rapid conversion of nutrients into biomass to enable cell proliferation. Indeed, most cancers have increased glucose uptake and lactic acid production. Furthermore, cancer cells have very dysregulated electrolyte balances, and in the interaction of the pH dynamics with electrolyte, dynamics is less well known. In this review, we highlight the interconnected roles of dysregulated pH dynamics and electrolytes imbalance in cancer initiation, progression, adaptation, and in determining the programming and reprogramming of tumor cell metabolism.

show abstract

“ The new pH-centric anticancer paradigm in Oncology and Medicine ” ; SCB, 2017

Cited by 26 publications

References 0 publications

Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New H+-Centered Anticancer Paradigm of the Late Post-Warburg Era

Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New H+-Centered Anticancer Paradigm of the Late Post-Warburg Era

Disturbances in H+ dynamics during environmental carcinogenesis

The Interplay of Dysregulated pH and Electrolyte Imbalance in Cancer

Contact Info

Product

Resources

About