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J. physiol. biochem ; 74(2): 223-234, mayo 2018. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-178979


Breast cancer (BC) is a persistent and impulsive metabolic disorder with the highest prevalence in women, worldwide. 7,12-Dimethylbenz(a)anthracene (DMBA) is a potent polyaromatic hydrocarbon (PAH)-based carcinogen producing mammary carcinomas in rats resembling the human hormone-dependent BC. 7,8-Dihydroxycoumarin (78DC) is a coumarin derivative that possesses diversified and favorable pharmacology profile to be considered in anticancer research against various malignancies. The present study was intended to investigate the antiproliferative and chemotherapeutic potentials of 78DC (20, 40, and 80 mg/kg BW) against DMBA (20 mg in olive oil)-induced mammary carcinoma Sprague-Dawley rats. We established the in silico approach for evaluation of the effect of 78DC on hormonal (estrogen receptor-α (ERα), progesterone receptor (PR)), growth factor receptors (EGFR and IGFR), 17Beta-hydroxysteroid dehydrogenase type 1 (17Beta -HD1), and aromatase. Effect of 78DC on estrogen synthesis, tumor growth, proliferation markers (Ki-67 and PCNA), cytokines (IL-10, IL-1 Beta, IL-12), chemokine (MCP-1), and cellular expressions of ERα, PR, EGFR, IGF1R, p-MAPK1/2, p-JNK1/2, p-Akt, 17Beta-HD1, and aromatase was evaluated in mammary carcinoma bearing SD rats. DMBA induces large tumor burden and histological alterations in mammary gland with a subsequent increase in ERα, PR, EGFR, IGF1R, Ki-67, proliferating cell nuclear antigen (PCNA ), cytokines, and chemokine expressions. This was also correlated with the changes in rapid cell differentiation and proliferation. In contrast, 78DC treatment to the cancer-bearing animals abbreviated these changes and revealed to possess antitumorigenic and antiproliferative potentials. Further, a significant decrease in expressions of ERα, PR, EGFR, IGFR, p-MAPK1/2, p-JNK1/2, p-Akt, 17Beta-HD1, and aromatase signifies a reduction in estrogen sensitivity and secondary signaling pathways that may contribute to the prevention of tumor growth. The current findings revealed that 78DC potentially reduce cancer cell proliferation and reverted mammary cancer-induced changes in experimental animals in a dose-dependent manner

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Humanos , Animais , Feminino , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Antineoplásicos/farmacologia , Carcinógenos/toxicidade , Neoplasias Mamárias Experimentais/prevenção & controle , Neoplasias Mamárias Experimentais/induzido quimicamente , Umbeliferonas/farmacologia , 17-Hidroxiesteroide Desidrogenases/metabolismo , Aromatase/metabolismo , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Relação Dose-Resposta a Droga , Receptores ErbB/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Antígeno Ki-67/metabolismo , Células MCF-7 , Neoplasias Mamárias Experimentais/patologia
J. physiol. biochem ; 68(3): 461-473, sept. 2012.
Artigo em Inglês | IBECS | ID: ibc-122334


Increased intracelullar hormone concentration levels have been shown to be the cause of several endocrine-related cancers including breast, prostate, endometrial, ovarian, cervix, testicular, thyroid, and osteosarcoma. Deregulated expression of steroidogenic enzymes in these tumors seems to be the source of a positive balance in active steroids that bind to the corresponding nuclear receptor, thus ultimately stimulating cell proliferation. Among these enzymes, 17 Beta-hydroxysteroid (..) (AU)

Humanos , Neoplasias das Glândulas Endócrinas/patologia , 17-Hidroxiesteroide Desidrogenases , Proliferação de Células