SMCT1 Cancer Research Results

SMCT1, SLC5A8: Click to Expand ⟱
Source:
Type:
SLC5A8 (also known as SMCT1) is a sodium-coupled monocarboxylate transporter.
SLC5A8 (SMCT1) is a sodium-coupled monocarboxylate transporter and a candidate tumor suppressor. It mediates uptake of butyrate, pyruvate, and related metabolites, enabling HDAC inhibition and promoting apoptosis / growth suppression in cancer cells. It is frequently silenced by DNA methylation, especially in colorectal cancer, and has also been implicated in breast, lung, cervical, gastric, thyroid, brain, and kidney cancers.
- Many studies suggest that SLC5A8 functions as a tumor suppressor. In normal tissues, SLC5A8 contributes to the cellular uptake of short-chain fatty acids (SCFAs) like butyrate. Butyrate is known to have histone deacetylase inhibitor activity, which can modulate gene expression in a way that suppresses tumor growth.
-In cancer, loss or silencing of SLC5A8 is often observed. Epigenetic mechanisms such as DNA hypermethylation of the SLC5A8 promoter region are commonly cited as a reason for its downregulation.

SLC5A8 is commonly downregulated in a variety of cancers. Its loss, often due to promoter hypermethylation, correlates with poorer outcomes in several tumor types, suggesting a tumor suppressor role. While sustained expression of SLC5A8 appears to be protective and is associated with a better prognosis in some cancers, the field is still evolving.

Inhibitors of DNA methylation induce reactivation of SLC5A8.
procaine is a DNA-demethylating agent with growth-inhibitory effects in human cancer cells.
Scientific Papers found: Click to Expand⟱
1885- DCA,    Role of SLC5A8, a plasma membrane transporter and a tumor suppressor, in the antitumor activity of dichloroacetate
- in-vitro, CRC, HCT116 - in-vitro, CRC, SW-620 - in-vitro, CRC, HT-29
SMCT1∅, SLC5A8 transports dichloroacetate very effectively with high affinity. This transporter is expressed in normal cells, but the expression is silenced in tumor cells via epigenetic mechanisms.
eff↓, lack of the SLC5A8 transporter makes tumor cells resistant to the antitumor activity of dichloroacetate.
eff↑, However, if the transporter is expressed in tumor cells ectopically, the cells become sensitive to the drug at low concentrations. This is evident in breast cancer cells, colon cancer cells, and prostate cancer cells.
eff↑, our findings suggest that combining dichloroacetate with a DNA methylation inhibitor would offer a means to reduce the doses of dichloroacetate to avoid detrimental effects associated with high doses but without compromising antitumor activity.
PDKs↓, Dichloroacetate is an inhibitor of pyruvate dehydrogenase kinase (PDK), which phosphorylates the E1α subunit of PDC and inactivates the complex
MMP↓, depolarization of the mitochondrial membrane,
Glycolysis↓, suppression of glycolysis
mitResp↑, enhancement of mitochondrial oxidation
ROS↑, production of reactive oxygen species,
eff↑, In control cells, which did not express the transporter, dichloroacetate did not have any significant effect. However, under identical conditions, SLC5A8-expressing cells underwent apoptosis to a marked extent. This phenomenon was seen in all three c


Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

mitResp↑, 1,   MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

Glycolysis↓, 1,   PDKs↓, 1,  

Barriers & Transport ⓘ

SMCT1∅, 1,  

Drug Metabolism & Resistance ⓘ

eff↓, 1,   eff↑, 3,  
Total Targets: 8

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: SMCT1, SLC5A8
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

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:1202  State#:%  Dir#:6
  wNotes=on  sortOrder:rid,rpid

 

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