Angiogenesis, invasion, and metastasis are the main events of cancer cells. JAK1/STAT3 is a key intracellular signaling transduction path, which controls the growth, differentiation, apoptosis, invasion, and angiogenesis in various cancer cells. The existing study explored the impact of AITC on the JAK-1/STAT-3 pathway in DMBAinjected rat mammary tumorigenesis. The mammary tumor was initiated through a single dose of 25 mg DMBA/rat through a subcutaneous injection administered near the mammary gland. We observed decreased body weight and augmented the total number of tumors, tumor incidence, tumor volume, well-developed tumor, and histopathological abnormalities in DMBA-injected rats and that were modulated after being treated with AITC. Staining of mammary tissues showed a high accumulation of collagen in DMBAtreated rats and it was normalized by the AITC treatment. Moreover, DMBA-induced mammary tissues showed up-regulated expressions of EGFR, pJAK-1, pSTAT-3, the nuclear fraction of STAT-3, and its associated products like VEGF, VEGFR2, HIF-1α, MMP-2, and MMP-9 and the down-regulated expressions of cytosolic STAT-3 and TIMP-2. Oral administration of AITC on DMBAtreated rats inhibits angiogenesis and invasion through modi ed these angiogenic and invasive markers. The nding of the current study is further con rmed by molecular docking analysis that shows a strong binding interaction between AITC with STAT-3 and cocrystal structure of STAT3 glide energy of -18.123 and − 72.246 (kcal/mole), respectively. Overall, the results suggested that AITC inhibits activation of the JAK-1/STAT-3 path, which subsequently prevents angiogenesis and invasion. It was recommended that AITC might develop a bene cial effect against breast cancer.
Angiogenesis, invasion, and metastasis are the main events of cancer cells. JAK1/STAT3 is a key intracellular signaling transduction path, which controls the growth, differentiation, apoptosis, invasion, and angiogenesis in various cancer cells. The existing study explored the impact of AITC on the JAK-1/STAT-3 pathway in DMBAinjected rat mammary tumorigenesis. The mammary tumor was initiated through a single dose of 25 mg DMBA/rat through a subcutaneous injection administered near the mammary gland. We observed decreased body weight and augmented the total number of tumors, tumor incidence, tumor volume, well-developed tumor, and histopathological abnormalities in DMBA-injected rats and that were modulated after being treated with AITC. Staining of mammary tissues showed a high accumulation of collagen in DMBAtreated rats and it was normalized by the AITC treatment. Moreover, DMBA-induced mammary tissues showed up-regulated expressions of EGFR, pJAK-1, pSTAT-3, the nuclear fraction of STAT-3, and its associated products like VEGF, VEGFR2, HIF-1α, MMP-2, and MMP-9 and the down-regulated expressions of cytosolic STAT-3 and TIMP-2. Oral administration of AITC on DMBAtreated rats inhibits angiogenesis and invasion through modified these angiogenic and invasive markers. The finding of the current study is further confirmed by molecular docking analysis that shows a strong binding interaction between AITC with STAT-3 and cocrystal structure of STAT3 glide energy of -18.123 and − 72.246 (kcal/mole), respectively. Overall, the results suggested that AITC inhibits activation of the JAK-1/STAT-3 path, which subsequently prevents angiogenesis and invasion. It was recommended that AITC might develop a beneficial effect against breast cancer.
The present study was aimed to evaluate the protective effect of 3, 3-diindolylmethane (DIM) on bisphenol A (BPA) induced estrogen signaling in the mammary glands of female Sprague-Dawley rats. Chronic administration of BPA (10 μg/kg/bw) to rats exerts rapid estrogenic action via GPR30 and activate cascade of signaling molecule which induce cell proliferation in the mammary gland. Western blot analysis of mammary tissues shows over expression of GPR30, SRC, RAS, PI3K and Akt proteins and immunohistochemical analysis reveals over expression of PCNA and no significant changes in ERs. Further, oral administration of DIM (5 mg/kg/bw), alternative days to BPA treated rats for the period of 12 weeks show significant decrease in the expression pattern of GPR30, SRC, RAS, PI3K, Akt and PCNA. The results of our study demonstrate that BPA induces rapid action via the over expression of proteins in non-genomic estrogen signaling pathway. Administration of DIM inhibits the action of BPA by modulating the expression of proteins involved in GPR30 cascade signaling pathway mediated cell proliferation in mammary glands of female rats.
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