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Cancer Prevention02:59

Cancer Prevention

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Several factors can increase the risk of cancer in an individual. About 50% of cancer cases can be prevented by adopting a healthy lifestyle, regular exercise, eating healthy, and following a modest cancer prevention diet. Epidemiological studies have consistently shown that populations with vegetable and fruit-rich diets have reduced the incidence of cancer. On the other hand, populations who have a diet rich in animal fat, red meat, junk food, or high calories are predisposed to cancer.
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The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
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Cancer Therapies02:49

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Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
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Inhibition of Cdk Activity02:34

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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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In the presence of oxidizing agents, phenols are oxidized to quinones. Quinones can be easily reduced back to phenols using mild reducing agents. The electron-donating hydroxyl group enhances the reactivity of the aromatic ring, enabling oxidation of the ring even in the absence of an α hydrogen.
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Oral anticoagulants are vital tools in preventing and treating blood clotting disorders. This diverse class of medications can be categorized as vitamin K antagonists, exemplified by warfarin, and direct thrombin inhibitors (DTIs), such as dabigatran, as well as factor Xa inhibitors, including rivaroxaban.
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Structural related oxidovanadium(IV)-flavonoid complexes. Influence on their anticancer effects.

Alexandra Velásquez Bravo1, Juan J Martínez Medina2, Libertad L López Tevez2

  • 1CEQUINOR, CONICET/UNLP, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Bv. 120 N° 1465, 1900 La Plata, Argentina.

Journal of Inorganic Biochemistry
|April 10, 2025
PubMed
Summary
This summary is machine-generated.

Oxidovanadium(IV) (VO) complexes with flavonoids show anticancer potential. VOtroxerutin and VOquercetin exhibit selective cytotoxicity against lung cancer cells by inducing oxidative stress, with VOtroxerutin demonstrating a favorable safety profile.

Keywords:
AnticancerFlavonoidsOxidative stressOxidovanadium(IV) complexesSafety profileSimilar coordination environment

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Area of Science:

  • Medicinal Chemistry
  • Biochemistry
  • Materials Science

Background:

  • Flavonoids possess antioxidant properties but can act as pro-oxidants in cancer cells, especially when complexed with metal ions.
  • Oxidovanadium(IV) (VO) complexes with flavonoids exhibit significant anticancer activity, influenced by ligand structure.
  • Troxerutin, a modified quercetin, has altered hydroxyl groups, potentially affecting its metal coordination and activity compared to quercetin.

Purpose of the Study:

  • To synthesize and characterize oxidovanadium(IV) complexes with troxerutin (VOtroxerutin) and quercetin (VOquercetin).
  • To investigate the relationship between the structure of these VO-flavonoid complexes and their anticancer activity.
  • To evaluate the cytotoxicity, selectivity, and safety profile of VOtroxerutin as a potential anticancer therapeutic.

Main Methods:

  • Synthesis and full characterization of VOtroxerutin and VOquercetin complexes using spectroscopic (FTIR, EPR, UV-Vis), elemental, thermal, and conductivity analyses.
  • In vitro cytotoxicity assays against A549 human lung cancer cells and HaCaT normal human keratinocytes.
  • Evaluation of pro-oxidant effects, mitochondrial membrane disruption, and safety profile (acute toxicity, mutagenicity) of VOtroxerutin.

Main Results:

  • Both VOtroxerutin and VOquercetin complexes demonstrated significant in vitro cytotoxicity against A549 lung cancer cells (32.1% and 39.5% viability inhibition, respectively, at 100 μM).
  • The complexes showed selectivity, with minimal effect on normal HaCaT keratinocytes (10% viability inhibition at 100 μM for VOtroxerutin).
  • Pro-oxidant activity was observed in cancer cells, leading to oxidative stress and mitochondrial damage; VOtroxerutin showed no acute toxicity or mutagenic effects.

Conclusions:

  • VO-flavonoid complexes, specifically VOtroxerutin and VOquercetin, possess promising anticancer potential due to their selective induction of oxidative stress in cancer cells.
  • The structural modifications in troxerutin, compared to quercetin, influence the complex's properties and therapeutic potential.
  • VOtroxerutin exhibits a favorable safety profile, supporting its development as a targeted anticancer therapy.