• Home
  • Search Results
  • Direct and indirect inactivation of tumor cell protective catalase by salicylic acid and anthocyanidins reactivates intercellular ROS signaling and allows for synergistic effects.

Direct and indirect inactivation of tumor cell protective catalase by salicylic acid and anthocyanidins reactivates intercellular ROS signaling and allows for synergistic effects.

Carcinogenesis (2015-02-06)
Katrin Scheit, Georg Bauer
ABSTRACT

Salicylic acid and anthocyanidins are known as plant-derived antioxidants, but also can provoke paradoxically seeming prooxidant effects in vitro. These prooxidant effects are connected to the potential of salicylic acid and anthocyanidins to induce apoptosis selectively in tumor cells in vitro and to inhibit tumor growth in animal models. Several epidemiological studies have shown that salicylic acid and its prodrug acetylsalicylic acid are tumor-preventive for humans. The mechanism of salicylic acid- and anthocyanidin-dependent antitumor effects has remained enigmatic so far. Extracellular apoptosis-inducing reactive oxygen species signaling through the NO/peroxynitrite and the HOCl signaling pathway specifically induces apoptosis in transformed cells. Tumor cells have acquired resistance against intercellular reactive oxygen species signaling through expression of membrane-associated catalase. Here, we show that salicylic acid and anthocyanidins inactivate tumor cell protective catalase and thus reactive apoptosis-inducing intercellular reactive oxygen species signaling of tumor cells and the mitochondrial pathway of apoptosis Salicylic acid inhibits catalase directly through its potential to transform compound I of catalase into the inactive compound II. In contrast, anthocyanidins provoke a complex mechanism for catalase inactivation that is initiated by anthocyanidin-mediated inhibition of NO dioxygenase. This allows the formation of extracellular singlet oxygen through the reaction between H(2)O(2) and peroxynitrite, amplification through a caspase8-dependent step and subsequent singlet oxygen-mediated inactivation of catalase. The combination of salicylic acid and anthocyanidins allows for a remarkable synergistic effect in apoptosis induction. This effect may be potentially useful to elaborate novel therapeutic approaches and crucial for the interpretation of epidemiological results related to the antitumor effects of secondary plant compounds.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Hydrochloric acid, ACS reagent, 37%
Sigma-Aldrich
Hydrochloric acid, ACS reagent, 37%
Supelco
Hydrogen chloride – 2-propanol solution, ~1.25 M HCl (T), for GC derivatization, LiChropur
Sigma-Aldrich
Salicylic acid, ACS reagent, ≥99.0%
Sigma-Aldrich
Hydrogen chloride solution, 4.0 M in dioxane
Sigma-Aldrich
Hydrochloric acid solution, 1.0 N, BioReagent, suitable for cell culture
Sigma-Aldrich
Hydrochloric acid, 36.5-38.0%, BioReagent, for molecular biology
Sigma-Aldrich
Hydrochloric acid, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., fuming, ≥37%, APHA: ≤10
Sigma-Aldrich
Taurine, ≥99%
Supelco
Hydrochloric acid solution, volumetric, 0.1 M HCl (0.1N), endotoxin free
Supelco
Salicylic acid, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Hydrogen chloride solution, 2.0 M in diethyl ether
Sigma-Aldrich
Hydrochloric acid, 37 wt. % in H2O, 99.999% trace metals basis
Sigma-Aldrich
3-Amino-1,2,4-triazole, ≥95% (TLC)
Sigma-Aldrich
Salicylic acid, suitable for plant cell culture
Supelco
Hydrogen chloride – methanol solution, ~1.25 m HCl (T), for GC derivatization, LiChropur
Sigma-Aldrich
Salicylic acid, ≥99%, FG
Sigma-Aldrich
Salicylic acid, puriss. p.a., ≥99.0% (T)
Sigma-Aldrich
Hydrogen chloride, ReagentPlus®, ≥99%
Sigma-Aldrich
Manganese, powder, ≥99.9% trace metals basis
Sigma-Aldrich
Taurine, suitable for cell culture, meets USP testing specifications
Sigma-Aldrich
Hydrochloric acid, meets analytical specification of Ph. Eur., BP, NF, fuming, 36.5-38%
Sigma-Aldrich
Hydrochloric acid solution, 32 wt. % in H2O, FCC
Sigma-Aldrich
Hydrochloric acid solution, ~6 M in H2O, for amino acid analysis
Sigma-Aldrich
Hydrogen chloride solution, 3 M in cyclopentyl methyl ether (CPME)
Supelco
Hydrogen chloride – ethanol solution, ~1.25 M HCl, for GC derivatization, LiChropur
Sigma-Aldrich
Salicylic acid, BioXtra, ≥99.0%
Sigma-Aldrich
Hydrogen chloride solution, 1.0 M in diethyl ether
Sigma-Aldrich
Hydrochloric acid, puriss., 24.5-26.0%
Histidine, European Pharmacopoeia (EP) Reference Standard