TS Cancer Research Results

TS, thymidylate synthase: Click to Expand ⟱
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Thymidylate synthase (TS) is a key enzyme responsible for catalyzing the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), a crucial step in the synthesis of thymidine—one of the four nucleotides required for DNA replication and repair.
Due to its essential role in DNA synthesis, TS is a critical target for chemotherapeutic agents such as 5-fluorouracil (5-FU) and other antifolates.
Many cancers exhibit elevated levels of TS expression compared to normal tissues.
High TS expression can contribute to rapid cell proliferation and tumor growth by ensuring a sufficient supply of thymidine for DNA synthesis.

Thymidylate synthase (TS) plays a central role in DNA synthesis and cell proliferation, making it a critical enzyme in cancer biology. Overexpression of TS is commonly observed in a range of tumor types and is associated with increased cellular proliferation, drug resistance, and generally poorer clinical outcomes. As both a therapeutic target and a prognostic marker, TS levels offer insight into tumor aggressiveness and potential responsiveness to chemotherapeutic agents.
Scientific Papers found: Click to Expand⟱
2263- dietMet,    Methionine Restriction and Cancer Biology
- Review, Var, NA
AntiCan↑, dependence of many tumor cells on an exogenous source of the sulfur amino acid, methionine, [9,10,11] makes dietary methionine restriction (MR) an exciting potential tool in the treatment of cancer.
TumCP↓, Proliferation and growth of several types of cancer cells are inhibited by MR,
TumCG↓,
selectivity↑, while normal cells are unaffected by limiting methionine as long as homocysteine is present
ChemoSen↓, MR has been shown to enhance efficacy of chemotherapy and radiation therapy in animal models
RadioS↑,
Insulin↓, MR may work by inhibiting prostate cancer cell proliferation, inhibiting the insulin/IGF-1 axis
*GlucoseCon↑, increase in tissue-specific glucose uptake measured during a hyperinsulinemic-euglycemic clamp
*ROS↓, MR does not increase oxidative stress, in part because MR enhances antioxidant capacity and increases proton leak in the liver, likely decreasing ROS production
*antiOx↑,
*GSH↑, ability of MR to increase GSH levels in red blood cells. Surprisingly, when methionine was restricted by 80% in the diet of rats, the level of GSH in the blood actually increased due to adaptations in sulfur-amino acid metabolism
GSH↑, However, GSH concentrations were reduced in the liver
eff↑, Of note, methionine restriction is effective when the non-essential amino acid, cysteine, is absent from the diet or media.
polyA↓, MR may work by inhibiting prostate cancer cell proliferation, inhibiting the insulin/IGF-1 axis, or by reducing polyamine synthesis. MR-induced depletion of polyamines
TS↓, MR selectively reduces TS activity in prostate cancer cells by ~80% within 48 h, but does not affect TS activity in normal prostate epithelial cells
Raf↓, MR inhibits Raf and Akt oncogenic pathways, while increasing caspase-9 and the mitochondrial pro-apoptotic protein, Bak
Akt↓,
Casp9↑,
Bak↑,
P21↑, MR upregulating p21 and p27 (cell cycle inhibitors that halt cell cycle progression) in LNCaP cells
p27/CDKN1B↑,
Insulin↓, MR-induced reduction in circulating insulin and IGF1, which have both been linked to tumor growth
IGF-1↓,

2264- dietMet,    Methionine restriction for cancer therapy: From preclinical studies to clinical trials
- Review, Var, NA
TumCP↓, methionine restriction (MR) reduces cancer cell proliferation via different mechanisms
*ROS?, MR lowers sulfur-containing metabolite levels, reduces oxidative stress, and enhances the immune response
ChemoSen↑, may sensitize tumors to chemo/radiotherapy
RadioS↑,
eff↑, therapeutic potential of MR lies in its ability to synergize with other therapies, enhancing overall antitumor efficacy.
ROS↑, increases ROS, weaking cancer cell defense (from graphical abstract). In colon cancer, MR increases oxidative stress, induces cell cycle arrest, and promotes the apoptosis of p53(Tumor Protein 53)-deleted cells
selectivity↑, methionine-depleted media significantly impaired the growth of malignant cells while leaving normal cell growth unchanged.
TS↓, MR also targets thymidylate synthase (TS), a key enzyme in nucleotide synthesis, enhancing the chemotherapeutic efficacy of 5-FU by lowering TS activity and expression
eff↑, duration of methionine deprivation can significantly affect the tumor cell response. Intermittent methionine deprivation appears particularly beneficial, enhancing tumor cell sensitivity to CD8+ T cell-mediated cytotoxicity

1329- EMD,    Aloe-emodin induces cell death through S-phase arrest and caspase-dependent pathways in human tongue squamous cancer SCC-4 cells
- in-vitro, Tong, SCC4
TumCCA↑, S-phase arrest
eff↓, The free radical scavenger N-acetylcysteine (NAC) and caspase inhibitors markedly blocked aloe-emodin-induced apoptosis
P53↑,
P21↑,
p27/CDKN1B↑,
cycA1/CCNA1↓,
cycE/CCNE↓,
TS↓,
CDC25↓, Cdc25A
AIF↑, promoted the release of apoptosis-inducing factor (AIF)
proCasp9↓,
Cyt‑c↑,
MMP↓,
Bax:Bcl2↑,
Casp3↑,
Casp9↑,

6563- Ger,  5-FU,    Geraniol, a component of plant essential oils, modulates DNA synthesis and potentiates 5-fluorouracil efficacy on human colon tumor xenografts
- vitro+vivo, Colon, SW-620 - in-vitro, Colon, Caco-2
TS↓, Geraniol (150 microM) but not 5-fluorouracil caused a 2-fold reduction of thymidylate synthase and thymidine kinase expression in cancer cells.
TK1↓,
ChemoSen↑, potentiates 5-fluorouracil efficacy
TumVol↓, combined administration of 5-fluorouracil (20 mg/kg) and geraniol (150 mg/kg) caused a 53% reduction of the tumor volume, whereas a 26% reduction was obtained with geraniol alone, 5-fluorouracil alone showed no effect.
OS↑, when geraniol and 5-FU were administered in combination the survival of mice was increased by 1.5 to 2-fold when compared to controls.

8096- KAE,  5-FU,    Synergistic effect of kaempferol and 5‑fluorouracil on the growth of colorectal cancer cells by regulating the PI3K/Akt signaling pathway
- in-vitro, CRC, HCT8 - in-vitro, CRC, HCT8
ChemoSen↑, The combination of kaempferol and 5‑FU was determined to be more effective in inhibiting cell viability than either of the agents alone.
TumCP↓, The inhibition of tumors in response to kaempferol and 5‑FU was associated with the reduction in proliferation ability and stimulation of apoptosis.
Apoptosis↓,
BAX↑, kaempferol and 5‑FU could significantly upregulate the expression levels of Bax and downregulate the expression levels of Bcl‑2 and TS
Bcl-2↓,
TS↓,
PI3K↓, Furthermore, the combination treatment greatly inhibited the activation of the PI3K/Akt pathway, suggesting the involvement of this pathway in the synergistic effects.
Akt↓,

8097- KAE,    The Phenolic compound Kaempferol overcomes 5-fluorouracil resistance in human resistant LS174 colon cancer cells
- in-vitro, CRC, LS174T
ChemoSen↑, Our results showed that only Kaempferol was able to chemo-sensitize 5-FU-resistant LS174-R cells.
tumCV↓, This phenolic compound combined with 5-FU exerted synergistic inhibitory effect on cell viability.
Apoptosis↑, combination enhanced the apoptosis and induced cell cycle arrest of both chemo-resistant and sensitive cells through impacting the expression levels of different cellular effectors.
TumCCA↑,
ROS↓, Kaempferol also blocked the production of reactive oxygen species (ROS) and modulated the expression of JAK/STAT3, MAPK, PI3K/AKT and NF-κB
Casp3↑, activation of caspase 3 and caspase 9 and cleavage of PARP
Casp9↑,
cl‑PARP↑,
p‑STAT3↓, Kaempferol alone or combined with 5-FU reduced the phosphorylated form of STAT3 and the one of the pro-survival kinase AKT and its target tumor suppressor FOXO3a transcription factor,
Akt↓,
FOXO3↓,
NF-kB↓, Our result also supports the inhibition of NF-κB in the refractive cancer cell line model
VEGF↓, interestingly, the combined treatment reduced also the production of VEGF-A (from 707 to 308 pg/ml) and IL-8 (from 319 to 127 pg/ml)
TS↓, TS and TK in the 5-FU-resistant cells, compared to sensitive LS174 cells (Fig. 7c), while the Kaempferol alone or in combination with 60 µM of 5-FU decreased the expression of the two proteins
TK1↓,


Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

GSH↑, 1,   ROS↓, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

AIF↑, 1,   CDC25↓, 1,   Insulin↓, 2,   MMP↓, 1,   Raf↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

polyA↓, 1,   TS↓, 6,  

Cell Death(tgid=5) ⓘ

Akt↓, 3,   Apoptosis↓, 1,   Apoptosis↑, 1,   Bak↑, 1,   BAX↑, 1,   Bax:Bcl2↑, 1,   Bcl-2↓, 1,   Casp3↑, 2,   Casp9↑, 3,   proCasp9↓, 1,   Cyt‑c↑, 1,   p27/CDKN1B↑, 2,  

Transcription & Epigenetics(tgid=7) ⓘ

tumCV↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

P53↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

cycA1/CCNA1↓, 1,   cycE/CCNE↓, 1,   P21↑, 2,   TumCCA↑, 2,  

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

FOXO3↓, 1,   IGF-1↓, 1,   PI3K↓, 1,   p‑STAT3↓, 1,   TK1↓, 2,   TumCG↓, 1,  

Migration(tgid=13) ⓘ

TumCP↓, 3,  

Angiogenesis & Vasculature(tgid=14) ⓘ

VEGF↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

NF-kB↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↓, 1,   ChemoSen↑, 4,   eff↓, 1,   eff↑, 3,   RadioS↑, 2,   selectivity↑, 2,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   OS↑, 1,   TumVol↓, 1,  
Total Targets: 47

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   GSH↑, 1,   ROS?, 1,   ROS↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

GlucoseCon↑, 1,  
Total Targets: 5

Scientific Paper Hit Count for: TS, thymidylate synthase
2 diet Methionine-Restricted Diet
2 5-fluorouracil
2 Kaempferol
1 Emodin
1 Geraniol
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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