ABSTRACT
Ovarian cancer is the deadliest gynecological cancer which rarely causes symptoms, and goes undetected until reaching the advanced stage of drug-resistant metastases. The cationic porphyrin meso-tetra(4-N-methylpyridyl)porphine (TMPyP) is a well-known photosensitizer (PS) used in photodyamic therapy (PDT) for curing cancer due to its strong affinity for DNA and high yield of reactive oxygen species (ROS) upon light activation. The practicality to irradiate tumor cells alone in the physiological system being slim (due to the close proximity of healthy cells and tumors), we looked for a variation in the PDT using a mixture of TMPyP with 1,5-dihydroxynapthalene (DHN) and Fe(III) ions at a mole ratio of 1:20:17 (drug combo) respectively in aqueous solution. The drug combo needs no photoactivation in H2O2 rich environment (mimicking the microenvironment of cancer/tumor), where it generates ȮH and juglone, the latter being a known potent anticancer agent. In vitro studies of the drug combo in drug resistant and sensitive ovarian cancer cell lines showed drastic growth inhibition and cell death compared to normal epithelial cells. The drug combo provides an effective and non-invasive alternative to conventional PDT, exploiting the cytosolic carcinogenic H2O2 to produce an efficient anticancer treatment. The unique action of cancer-specific cytotoxicity arises from the redox chemistry involving activation of Fe(III) as the oxidizing agent to generate juglone, which utilizes the cytosolic ROS in cancer cells against itself.
Subject(s)
Antineoplastic Agents/pharmacology , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Acids/metabolism , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Female , Fibroblasts/drug effects , Fibroblasts/metabolism , Humans , Hydrogen Peroxide/metabolism , Mice , Naphthols/pharmacology , Naphthoquinones/pharmacology , Oxidation-Reduction , Porphyrins/pharmacology , Spectrometry, FluorescenceABSTRACT
Here, we report an experimental study of the effect of toxic metal ions on photosensitized singlet oxygen generation for photodegradation of PAH derivatives, Anthracene-9,10-dipropionic acid disodium salt (ADPA) and 1,5-dihydroxynapthalene (DHN) and photoinactivation of Escherichia coli bacteria by using cationic meso-tetra(N-methyl-4-pyridyl)porphine tetrachloride (TMPyP) as a singlet oxygen photosensitizer. Three s-block metals ions, such as Na+ , K+ and Ca2+ and five toxic metals such as Cd2+ , Cu2+ , Hg2+ , Zn2+ and Pb2+ were studied. The s-block metal ions showed no change in the rate of photodegradation of ADPA or DHN by TMPyP, whereas a dramatic change in the photodegradation of ADPA and DHN was observed in the presence of toxic metals. The maximum photodegradation rate constants of ADPA and DHN were observed for Cd2+ ions [(3.91 ± 0.20) × 10-3 s-1 and (7.18 ± 0.35) × 10-4 s-1 , respectively]. Strikingly, the photodegradation of ADPA and DHN was almost completely inhibited in the presence of Hg2+ ions and Cu2+ ions. A complete inhibition of growth of E. coli was observed upon visible light irradiation of E. coli solutions with TMPyP and toxic metal ions particularly, Cd2+ , Hg2+ , Zn2+ and Pb2+ ions, except for Cu2+ ions where a significantly slow inhibition of E. coli's growth was observed.
