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1.
Curr Top Med Chem ; 22(30): 2474-2482, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36082856

RESUMO

Polyhydroxy compounds are secondary metabolites that are ubiquitous in plants of higher genera. They possess therapeutic properties against a wide spectrum of diseases, including cancers, neurodegenerative disorders, atherosclerosis, as well as cardiovascular disease. The phytochemical flavonol (a type of flavonoid) kaempferol (KMP) (3,5,7-trihydroxy-2-(4-hydroxyphenyl)- 4Hchromen-4-one) is abundant in cruciferous vegetables, including broccoli, kale, spinach, and watercress, as well as in herbs like dill, chives, and tarragon. KMP is predominantly hydrophobic in nature due to its diphenylpropane structure (a characteristic feature of flavonoids). Recent findings have indicated the promise of applying KMP in disease prevention due to its potential antioxidant, antimutagenic, antifungal, and antiviral activities. In the literature, there is evidence that KMP exerts its anticancer effects by modulating critical elements in cellular signal transduction pathways linked to apoptosis, inflammation, angiogenesis, and metastasis in cancer cells without affecting the viability of normal cells. It has been shown that KMP triggers cancer cell death by several mechanisms, including cell cycle arrest, caspase activation, metabolic alteration, and impacting human telomerase reverse-transcriptase gene expression. This review is aimed at providing critical insights into the influence of KMP on the intracellular cascades that regulate metabolism and signaling in breast, ovarian, and cervical cancer cells.


Assuntos
Quempferóis , Neoplasias , Humanos , Quempferóis/farmacologia , Quempferóis/química , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Transdução de Sinais , Antioxidantes/farmacologia , Inflamação/tratamento farmacológico , Apoptose
2.
Biochem Biophys Res Commun ; 592: 38-43, 2022 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-35026603

RESUMO

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 È®H 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.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Ácidos/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Camundongos , Naftóis/farmacologia , Naftoquinonas/farmacologia , Oxirredução , Porfirinas/farmacologia , Espectrometria de Fluorescência
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