SHMT2-mediated mitochondrial serine metabolism drives 5-FU resistance by fueling nucleotide biosynthesis

Pranzini, Erica; Pardella, Elisa; Muccillo, Livio; Leo, Angela; Nesi, Ilaria; Santi, Alice; Parri, Matteo; Zhang, Tong; Uribe, Alejandro Huerta; Lottini, Tiziano; Sabatino, Lina; Caselli, Anna; Arcangeli, Annarosa; Raugei, Giovanni; Colantuoni, Vittorio; Cirri, Paolo; Chiarugi, Paola; Maddocks, Oliver D.K.; Paoli, Paolo De; Taddei, Maria Letizia

doi:10.1016/j.celrep.2022.111233

Cited by 41 publications

(35 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Their data show that after 48 hours, the 5-FU IC50 for HCT-116 and HT-29 is around 3.2 µM and 1.6 µM, respectively. 32 While our results for S1, after 24 hours show 5.24 µM for HCT-116 and 3.185 µM for HT-29, respectively, for the half-maximal inhibitory concentration (IC50). The effect of complexing N - carbene ligand with silver(I) was studied by Huque et al revealed that the Ag-complex increase the efficiency against the HCT 116 and HT29 cell lines.…”

Section: Resultsmentioning

confidence: 55%

Synthesis of Gingerol-Metals Complex and in-vitro Cytotoxic Activity on Human Colon Cancer Cell Line

Khdary¹,

Alangari²,

Katubi³

et al. 2023

CMAR

View full text Add to dashboard Cite

Introduction Herbs are excellent sources of medicinal substances, and their curative abilities have been recognized to treat many ailments and are used for example as antioxidants, analgesics, anti-inflammatories, antipyretics, and many other medicinal uses. The properties of natural compounds and their health effects have been studied extensively, especially those that originate from plant sources such as ginger. The ginger plant contains many chemical compounds, such as 6-gingerol, which is characterized by containing active groups such as carbonyl and hydroxide, which can be attached to metal molecules. This is what was done in this study, where the formation of complexes with a group of metals was studied and their effect on cancer cells was investigated. These complexes will open new horizons for further study of medicinal uses. Methods The synthesis of gingerol-metal complexes was carried out by conjugating gingerol molecules with Ag, Au, Cd, Co, Cu, Ni, and Zn metal ions. The extracted gingerol was transferred to culture tubes and deionized water-DMSO were added followed by sonication. The tubes were incubated at 90°C for two days as well as the control sample. The samples were then filtered and the complex solutions were transferred into new tubes for further studies. Different characterization techniques such as FT-IR, UV-vis spectroscopy, FESEM, and EDX are used to confirm the formation of the complexes. The in vitro of the complexes was tested by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay against the human colorectal cancer cell lines HCT116 and HT29 which exhibited strong cytotoxicity. Results The gingerol-metal complexes showed an enhancement as an anticancer agent compared to the control. The in vitro anticancer activity showed that the Ag-gingerol complex showed the most activity among the other complexes. Discussion Gingerol-metal complexes can inhibit cancer cells, noting that the potency of the complex depends on the type of metal used.

show abstract

Section: Resultsmentioning

confidence: 55%

Synthesis of Gingerol-Metals Complex and in-vitro Cytotoxic Activity on Human Colon Cancer Cell Line

Khdary¹,

Alangari²,

Katubi³

et al. 2023

CMAR

View full text Add to dashboard Cite

show abstract

“…The plate was then transferred in a non-CO 2 incubator for 1 h at 37 °C to pre-equilibrate the cells before analysis. An XF Mito Stress Test was performed to assay the cells’ ability to exploit mitochondrial oxidative metabolism, according to the manufacturer’s instructions [ 53 ]. The oxygen consumption rate (OCR) was evaluated after the injection of a sequence of compounds that interfere with the electron transport chain: oligomycin (1 μM), carbonyl cyanide-4 (trifluoromethoxy) phenylhydrazone (FCCP) (1 μM), and Rotenone/Antimycin A (0.5 μM).…”

Section: Methodsmentioning

confidence: 99%

Evidence of Insulin-Sensitizing and Mimetic Activity of the Sesquiterpene Quinone Avarone, a Protein Tyrosine Phosphatase 1B and Aldose Reductase Dual Targeting Agent from the Marine Sponge Dysidea avara

et al. 2023

Self Cite

View full text Add to dashboard Cite

Type 2 diabetes mellitus (T2DM) is a complex disease characterized by impaired glucose homeostasis and serious long-term complications. First-line therapeutic options for T2DM treatment are monodrug therapies, often replaced by multidrug therapies to ensure that non-responding patients maintain target glycemia levels. The use of multitarget drugs instead of mono- or multidrug therapies has been emerging as a main strategy to treat multifactorial diseases, including T2DM. Therefore, modern drug discovery in its early stages aims to identify potential modulators for multiple targets; for this purpose, exploration of the chemical space of natural products represents a powerful tool. Our study demonstrates that avarone, a sesquiterpene quinone obtained from the sponge Dysidea avara, is capable of inhibiting in vitro PTP1B, the main negative regulator of the insulin receptor, while it improves insulin sensitivity, and mitochondria activity in C2C12 cells. We observe that when avarone is administered alone, it acts as an insulin-mimetic agent. In addition, we show that avarone acts as a tight binding inhibitor of aldose reductase (AKR1B1), the enzyme involved in the development of diabetic complications. Overall, avarone could be proposed as a novel natural hit to be developed as a multitarget drug for diabetes and its pathological complications.

show abstract

“…Cells were then incubated in a non-CO 2 incubator for 1 h at 37 °C to pre-equilibrate the cells before analysis. An XF Mito Stress Test was performed to assay the cells’ ability to exploit mitochondrial oxidative metabolism, according to the manufacturer’s instructions . Protein quantification was used to normalize the results.…”

Section: Methodsmentioning

confidence: 99%

“…An XF Mito Stress Test was performed to assay the cells' ability to exploit mitochondrial oxidative metabolism, according to the manufacturer's instructions. 68 Protein quantification was used to normalize the results. All tests were carried out in quadruplicate.…”

Section: S ) -N -{ 2 -[ ( 1 1 ′ -B I P H E N Y L ) -4 -Y L O X Y ] -...mentioning

confidence: 99%

A New Antidiabetic Agent Showing Short- and Long-Term Effects Due to Peroxisome Proliferator-Activated Receptor Alpha/Gamma Dual Agonism and Mitochondrial Pyruvate Carrier Inhibition

et al. 2023

Self Cite

View full text Add to dashboard Cite

A new series of analogues or derivatives of the previously reported PPARα/γ dual agonist LT175 allowed the identification of ligand 10, which was able to potently activate both PPARα and -γ subtypes as full and partial agonists, respectively. Docking studies were performed to provide a molecular explanation for this different behavior on the two different targets.In vivo experiments showed that this compound induced a significant reduction in blood glucose and lipid levels in an STZinduced diabetic mouse model displaying no toxic effects on bone, kidney, and liver. By examining in depth the antihyperglycemic activity of 10, we found out that it produced a slight but significant inhibition of the mitochondrial pyruvate carrier, acting also through insulin-independent mechanisms. This is the first example of a PPARα/γ dual agonist reported to show this inhibitory effect representing, therefore, the potential lead of a new class of drugs for treatment of dyslipidemic type 2 diabetes.

show abstract

SHMT2-mediated mitochondrial serine metabolism drives 5-FU resistance by fueling nucleotide biosynthesis

Cited by 41 publications

References 81 publications

Synthesis of Gingerol-Metals Complex and in-vitro Cytotoxic Activity on Human Colon Cancer Cell Line

Synthesis of Gingerol-Metals Complex and in-vitro Cytotoxic Activity on Human Colon Cancer Cell Line

Evidence of Insulin-Sensitizing and Mimetic Activity of the Sesquiterpene Quinone Avarone, a Protein Tyrosine Phosphatase 1B and Aldose Reductase Dual Targeting Agent from the Marine Sponge Dysidea avara

A New Antidiabetic Agent Showing Short- and Long-Term Effects Due to Peroxisome Proliferator-Activated Receptor Alpha/Gamma Dual Agonism and Mitochondrial Pyruvate Carrier Inhibition

Contact Info

Product

Resources

About