pH Cancer Research Results

pH, : Click to Expand ⟱
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Tumor Microenvironment: Cancer cells often thrive in a more acidic environment compared to normal cells. This is partly due to the metabolic processes of cancer cells, which can produce lactic acid and other acidic byproducts. The acidic microenvironment can promote tumor growth and invasion.
Many tumors exhibit an acidic microenvironment. This is largely due to the high rate of glycolysis (often referred to as the Warburg effect), even in the presence of oxygen, leading to lactate production. Acidification is thought to promote invasion, metastasis, and resistance to certain chemotherapies.
The body maintains a relatively stable pH in the blood (around 7.4). However, the pH of tissues can vary, and tumors can exhibit a lower pH.

-Normal tissues have a higher extracellular pH than intracellular pH, in cancer is exactly the opposite. (inversion of the pH gradient).

Cancer cells often overexpress proton pumps (such as V-ATPase) and transporters that actively extrude protons (H⁺) to maintain an intracellular pH conducive to their growth.
Inhibiting these pumps can lead to intracellular acidification and potentially induce apoptosis or render cancer cells more vulnerable to other treatments.
Normal pH levels in the body:
Nasal: ~6.3 pH
Mouth/saliva: 6.2-7.6 pH
Stomach: 1-3 pH
Small Intestine: 5.9-6.8 pH
Colon/Large Intestine: 6.8-7 pH


Scientific Papers found: Click to Expand⟱
6683- DCA,    Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts
- Review, Var, NA
PDK1↓, classic DCA target, pyruvate dehydrogenase kinase
lactateProd↓, reduce lactic acid production which would push the cell towards oxidative phosphorylation: this would be the supposed function of dichloroacetate (DCA).
Apoptosis↑, They found that DCA induced apoptosis and decreased proliferation by restoring mitochondrial oxidative metabolism, without toxicity to normal cells.
TumCP↓,
selectivity↑,
other↝, many clinics, usually called “DCA Clinics” have opened, mainly in Canada and Germany.
Dose↝, DCA is sold over the counter and is produced by many laboratories. The quality of the product from these laboratories is not well established. These particulars explain many of the doubts about DCA’s real value as a therapeutic tool.
BioAv↑, DCA is an orally available molecule that is quickly and almost completely absorbed by the digestive system
Half-Life↓, With a 10 mg/kg infusion the maximum plasma concentration achieved was between 19.9 μg/ml and 24.7 μg/ml with a half life of only 20 minutes. If the infused dose was increased to 20 mg/kg the plasma concentration was between 57.3 and 74.9 μg/ml with
Glycolysis↓, facilitates the switch from a glycolytic to an oxidative metabolism.
OXPHOS↑,
Casp↑, onversion to an oxidative metabolism by DCA, is an increase in caspase-mediated apoptosis
i-pH↓, pHi decreases (at least temporarily).
COX2↑, DCA increases the expression of COX2 and the latter increases tumor resistance to DCA. Therefore, a possible integrated treatment could be COX2 inhibitor co-administered with DCA
Hif1a↓, DCA suppresses HIF-1α activity and angiogenesis through the inhibition of PDK-II
angioG↓,
HMG-CoA↓, figure 7
GSTZ1↓,
OCR↑,
lipoGen↓,
fatigue↓,
survivin↓, Survivin (an inhibitor of apoptosis) expression was decreased and miR-375 (a microRNA which acts as a tumor suppressor) levels were increased.
miR-375↑,
eff↓, African Americans are known to respond poorly to therapy compared with Caucasian American patients.
CSCs↓, DCA can inhibit the cancer stem cell like characteristics of the cells and strongly influenced the metabolic pathway of the cells causing a shift from glycolysis to oxidative phosphorylation.
TumAuto↑, DCA induced autophagy in human colon cancer cells with ROS production and mTOR inhibition,
mTOR↓,
TumCI↓, DCA induced apoptosis, inhibited invasion, and angiogenesis. In mouse experiments in vivo with the melanoma allografts, DCA reduced volume and weight of tumors.
TumVol↓,
TumW↓,
ATP↓, DCA alone reduced glycolytic activity and intracellular ATP levels and inhibited cellular growth in melanoma cells.
Warburg↓, DCA was also found to interrupt the Warburg effect and decreased proliferation.
eff↑, The co-application of metformin and DCA suppressed human liver cancer cell proliferation inducing apoptosis through inhibition of mTORC1 and increased ROS in vitro and in vivo
e-pH↑, when measuring extracellular pH in vivo found that an initial increase in extracellular pH of tumors in mice when treated with DCA.
eff↑, To avoid the development of this type of metabolic resistance DCA should be given simultaneously with other metabolic drugs such as metformin [327] or 2 deoxyglucose.
eff↑, chronic co-administration of DCA with sodium bicarbonate to tumor bearing mice prolonged survival
other↝, High doses of thiamin (vit B1) have effects similar to those of DCA: reduced PDH phosphorylation, reduced lactate prod and increased casp3 activity with reduced proliferation in colon cancer cells. can vitB1 replace DCA as a nontoxic PDK inhibitor?
RadioS↑, Dong et al. [380] found that DCA radiosensitized esophageal carcinoma cells in vitro and in vivo through increased ROS accumulation.
toxicity↓, 25 mg/Kg/day may show a mild sedative effect or drowsiness. The most serious published side effect is reversible peripheral neuropathy
Dose↝, 10 to 50 mg/kg body weight/day has been found to be a safe dose. However, single nucleotide polymorphisms (SNPs) in the gene of the enzyme GSTZ1 cause difficulties in establishing a universal dose [409] as noted above.
eff↑, There is strong evidence showing that the association of metformin and DCA has significant cytotoxic effects.
eff↑, To this approach we must add a third compound: a COX2 inhibitor like celecoxib to decrease COX2 expression induced by DCA.
eff↑, the triple association of DCA, metformin and celecoxib, which has never been experimentally tested in patients, deserves well planned phase II clinical trials.
toxicity↝, DCA will never become a stand-alone chemotherapeutic compound. The fundamental reason for this statement is that the drug can only reach micromolar blood concentrations without toxicity and requires millimolar levels to be cytotoxic.
eff↓, DCA should not be used in association with allopurinol, NSAIDs, or flavonoids because they reduce cellular DCA uptake.

1884- DCA,  Sal,    Dichloroacetate and Salinomycin Exert a Synergistic Cytotoxic Effect in Colorectal Cancer Cell Lines
- in-vitro, CRC, DLD1 - in-vitro, CRC, HCT116
eff↑, The effect of combination of dichloracetate and salinomycin on multicellular spheroid size was stronger than the sum of both monotherapies, particularly in HCT116 cells
pH↓, and in contrast, it is not related to dichloroacetate-induced reduction of intracellular pH
PDKs↓, Dichloroacetate (DCA) is a small synthetic molecule that is known as a pyruvate dehydrogenase kinase inhibitor. Its anticancer properties involve reversing the Warburg effect by switching ATP production back to oxidative phosphorylation
Warburg↓,

6701- DFC,    Intracellular pH and calcium signaling as molecular targets of diclofenac-induced apoptosis against colon cancer
- in-vivo, Colon, NA
COX2↓, Diclofenac, a preferential cyclooxygenase-2 inhibitor, was used at the anti-inflammatory dose (8 mg/kg body weight) for chemoprevention.
Inflam↓,
chemoPv↑,
Apoptosis↑, Diclofenac promoted apoptosis in colonocytes when coadministered with DMH and also ameliorated the changes observed in the above parameters, confirming these mechanisms as early events for the onset of apoptosis in cancer cells.
pH↓, The control group and the diclofenac only group had a more acidic pH.
ROS↑, Coadministration of diclofenac with DMH significantly increased the number of cells showing green fluorescence; that is, it increased the production of ROS in colonocytes.
Ca+2↑, Cells from the DMH-treated and diclofenac-treated groups, however, showed improved Ca 2 + levels in isolated colonocytes, as shown by both fura-2 AM and CTC assays.
MMP↓, Simultaneous treatment of DMH with diclofenac led to a marked decrease in the number of cells with high membrane potential and thus in a loss of mitochondrial membrane potential
APAF1↑, Diclofenac was also able to revive the reduced level of Apaf-1 when administered simultaneously with DMH.

1612- EA,    Negative Effect of Ellagic Acid on Cytosolic pH Regulation and Glycolytic Flux in Human Endometrial Cancer Cell
- in-vitro, EC, NA
NHE1↓, 48 hour treatment with Ellagic acid (20 µM) significantly decreased NHE1 transcript levels by 75%, NHE1 protein abundance by 95%
i-pH↓, pHi from 7.24 ± 0.01 to 7.02 ± 0.01
ROS↓, ROS by 82%
GlucoseCon↓, glucose uptake by 58%
NHE1↓, Treatment with EA is followed by a significant decline of NHE1 transcript levels, NHE1 protein abundance, and Na+/H+ exchanger activity.
Glycolysis↓, EA down-regulates expression and function of the Na+/H+ exchanger, decreases cytosolic acidification with subsequent impairment of glycolysis

645- EGCG,    The Effect of Ultrasound, Oxygen and Sunlight on the Stability of (−)-Epigallocatechin Gallate
- Analysis, NA, NA
eff↑, Without oxygen, EGCG in aqueous solution was rather stable
pH↓, acidic environments enhance the stability of EGCG

995- MEL,    Melatonin Treatment Triggers Metabolic and Intracellular pH Imbalance in Glioblastoma
- vitro+vivo, GBM, NA
LDHA↓,
MCT4↓,
lactateProd↓,
i-pH↓, decrease in intracellular pH: melatonin treatment induced a pH reversal with intracellular acidosis parallel to a downregulation in glycolysis in GBM.
ROS↑,
ATP↓,
TumCD↑, cytotoxic effects on GBM were due, at least in part, to intracellular pH modulation
TumCCA↑, cell cycle arrest at G0/G1 in both GBM1A and QNS120 and G2/M in GBM1A
PDH↓, decrease in pyruvate dehydrogenase (PDH) expression for both cell lines at aMT 3.0 mM
Glycolysis↓,
GlucoseCon↓,
TumCG↓, in vivo

5253- NCL,    Niclosamide: Beyond an antihelminthic drug
- Review, Var, NA
TumCP↓, Niclosamide was found to inhibit adrenocortical carcinoma cellular proliferation, which was associated with apoptosis, reduction of epithelial-to-mesenchymal transition and β-catenin levels.
Apoptosis↑,
EMT↓,
β-catenin/ZEB1↓,
TumCG↓, Oral administration of niclosamide led to tumor growth inhibition with no observed toxicity.
toxicity↓,
Wnt↓, Lu et al. reported that niclosamide inhibits Wnt/β-catenin signaling by promoting Wnt co-receptor LRP6 degradation in breast cancer cells [11].
LRP6↓,
eff↑, niclosamide acts synergistically with a monoclonal antibody that specifically activates TRAIL death receptor 5 to inhibit tumor growth of basal-like breast cancers [12].
DR5↑,
mTORC1↓,
pH↓, Niclosamide lowered the cytoplasmic pH and may indirectly lead to inhibition of mTORC1 signaling [13]
CSCs↓, Niclosamide also was found to prevent the conversion of non-breast cancer stem cells into cancer stem cells
IL6↓, This mechanism is associated with inhibition of the IL6-JAK1-STAT3 signal transduction pathway
JAK1↓,
STAT3↓, Ren et al. identified niclosamide as a potent STAT3 inhibitor able to suppress STAT3 transcriptional activity
ChemoSen↑, niclosamide alone or in combination with cisplatin represses the growth of xenografts of cisplatin-resistant triple-negative breast cancer cells.
TumCG↓, Niclosamide inhibited growth of colon cancer cells from human patients both in vitro and in vivo, regardless of mutations in APC [24].
tumCV↓, niclosamide selectively inhibited glioblastoma cell viability [29]. Detailed mechanism studies revealed that niclosamide suppressed the Wnt, Notch, mTOR, and NF-κB signaling pathways.
NOTCH↓,
NF-kB↓,
EGFR↓, Li et al. reported that inhibition of EGFR by erlotinib, an FDA-approved therapeutic agent, led to activation of STAT3 signaling in head and neck cancer cells
ROS↑, niclosamide inhibits TNF-α-induced NF-κB–dependent reporter activity and increased the levels of reactive oxygen species (ROS) in AML cells.
RadioS↑, niclosamide enhanced radiosensitivity of the non-small cell lung cancer cell line H1299.
cFos↓, inhibit osteosarcoma cell proliferation, migration, and survival. This inhibitory effect is associated with decreased expression of c-Fos, c-Jun. E2F1, and c-Myc.
cJun↓,
E2Fs↓,
cMyc↓,
Half-Life↓, Niclosamide exhibits a short half-life (6.0 ± 0.8 h). Niclosamide was rapidly absorbed with a Tmax of less than 30 min. The Cmax is 354 ± 152 ng/mL.
BioAv↝, AUC and bioavailability were 429 ± 100 and 10%, respectively. In order to make more effective use of niclosamide, additional work needs to be done to improve its solubility, absorption and systemic bioavailability.

6765- ProBio,    Probiotics
*GutMicro↑, hese mechanisms include the inhibition of the growth of pathogenic microorganisms in the gastrointestinal tract (by fostering colonization resistance, improving intestinal transit, producing antimicrobial substances, or helping normalize a perturbed
*AntiBio↑,
*pH↓, and the reduction of luminal pH in the colon
*Diar↓, Some systematic reviews and meta-analyses report that starting certain probiotic treatments within 2 days of the first antibiotic dose helps reduce the risk of antibiotic-associated diarrhea in specific patient populations.

4726- Se,  Oxy,    Oxygen therapy accelerates apoptosis induced by selenium compounds via regulating Nrf2/MAPK signaling pathway in hepatocellular carcinoma
- in-vivo, HCC, NA
eff↝, Selenium has good antitumor effects in vitro, but the hypoxic microenvironment in solid tumors makes its clinical efficacy unsatisfactory.
NRF2↓, We found that, in contrast to hypoxia, the hyperoxic environment facilitated the H2Se, produced by the selenium metabolism in cells, to be rapidly oxidized to generate H2O2, leading to inhibit the expression level of Nrf2
p‑p38↑, and to increase that of phosphorylation of p38 and MKK4, resulting in inhibiting autophagy and accelerating apoptosis
Apoptosis↑,
eff↑, These findings highlight oxygen can significantly enhance the anti-HCC effect of selenium compounds through regulating the Nrf2 and MAPK signaling pathways
TumVol↓, The results showed that hyperoxia could improve the efficacy of Na2SeO3 and CysSeSeCys in the treatment of HCC, enhance the death rate of HepG2 cells, and further reduce the tumor volume in mice
other↝, These results also suggest that the anticancer mechanism of selenium compounds may be different in different oxygen environments.
toxicity↓, staining results of the liver and kidney of mice showed that the selenium compound combined with oxygen therapy did not show toxicity or side effects on normal organs
Dose↝, therapeutic effect reached the level of the 5 mg/kg selenium compound treatment group
NRF2↝, The results showed that in the 1 % O2 environment, the two selenium compounds promoted the expression of Nrf2, and the Nrf2 level gradually decreased with increasing oxygen concentration.
HO-1↓, The expression of HO-1, CAT and SOD also showed a decreasing trend with increasing oxygen concentration
Catalase↓,
SOD↓,
e-pH↓, The results showed that the extracellular pH value decreased after treatment with selenium compounds for 48 h
pH∅, However, there was no significant change in extracellular pH value in the selenium compound treatment group compared with the oxygen alone group
MAPK↑, Selenium combined with oxygen therapy accelerates cell apoptosis by activating the MAPK signaling pathway
eff↑, In summary, oxygen can significantly enhance the antihepatocellular carcinoma effect of selenium compounds

636- VitC,    Acute Effects of Vitamin C Exposure On Colonic Crypts: Direct Modulation of pH Regulation
- in-vivo, NA, NA
pH↓, Acute addition of Vitamin C to the basolateral membrane maintains low intracellular pH for a longer period which could halt and/or prevent tumor formation.
SVCT-2∅, Vitamin C could potentially be transported via SVCT2


Showing Research Papers: 1 to 10 of 10

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 10

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

miR-375↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

Catalase↓, 1,   GSTZ1↓, 1,   HO-1↓, 1,   NRF2↓, 1,   NRF2↝, 1,   OXPHOS↑, 1,   ROS↓, 1,   ROS↑, 3,   SOD↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 2,   MMP↓, 1,   OCR↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

cMyc↓, 1,   GlucoseCon↓, 2,   Glycolysis↓, 3,   HMG-CoA↓, 1,   lactateProd↓, 2,   LDHA↓, 1,   lipoGen↓, 1,   MCT4↓, 1,   PDH↓, 1,   PDK1↓, 1,   PDKs↓, 1,   Warburg↓, 2,  

Cell Death(tgid=5) ⓘ

APAF1↑, 1,   Apoptosis↑, 4,   Casp↑, 1,   DR5↑, 1,   MAPK↑, 1,   p‑p38↑, 1,   survivin↓, 1,   TumCD↑, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

cJun↓, 1,   other↝, 3,   tumCV↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

TumAuto↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

E2Fs↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

cFos↓, 1,   CSCs↓, 2,   EMT↓, 1,   LRP6↓, 1,   mTOR↓, 1,   mTORC1↓, 1,   NOTCH↓, 1,   STAT3↓, 1,   TumCG↓, 3,   Wnt↓, 1,  

Migration(tgid=13) ⓘ

Ca+2↑, 1,   TumCI↓, 1,   TumCP↓, 2,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   EGFR↓, 1,   Hif1a↓, 1,  

Barriers & Transport(tgid=15) ⓘ

NHE1↓, 2,   SVCT-2∅, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2↓, 1,   COX2↑, 1,   IL6↓, 1,   Inflam↓, 1,   JAK1↓, 1,   NF-kB↓, 1,  

Cellular Microenvironment(tgid=17) ⓘ

pH↓, 5,   pH∅, 1,   e-pH↓, 1,   e-pH↑, 1,   i-pH↓, 3,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1,   BioAv↝, 1,   ChemoSen↑, 1,   Dose↝, 3,   eff↓, 2,   eff↑, 11,   eff↝, 1,   Half-Life↓, 2,   RadioS↑, 2,   selectivity↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

EGFR↓, 1,   IL6↓, 1,  

Functional Outcomes(tgid=23) ⓘ

chemoPv↑, 1,   fatigue↓, 1,   toxicity↓, 3,   toxicity↝, 1,   TumVol↓, 2,   TumW↓, 1,  
Total Targets: 87

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

AntiBio↑, 1,  

Cellular Microenvironment(tgid=17) ⓘ

pH↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

GutMicro↑, 1,  

Infection & Microbiome(tgid=24) ⓘ

Diar↓, 1,  
Total Targets: 4

Scientific Paper Hit Count for: pH,
2 Dichloroacetate
1 salinomycin
1 Diclofenac
1 Ellagic acid
1 EGCG (Epigallocatechin Gallate)
1 Melatonin
1 Niclosamide (Niclocide)
1 probiotics
1 Selenium
1 Oxygen, Hyperbaric
1 Vitamin C (Ascorbic Acid)
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

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