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Melatonin Attenuates Her-2, p38 MAPK, p-AKT, and mTOR Levels in Ovarian Carcinoma of Ethanol-Preferring Rats.

Ferreira GM, Martinez M, Camargo IC, Domeniconi RF, Martinez FE, Chuffa LG - J Cancer (2014)

Bottom Line: While Mel therapy was unable to reduce Her-4 and phosphoinositide 3-kinase (PI3K) levels, it was able to suppress the OC-related increase in the levels of the Her-2, p38 mitogen-activated protein kinases (p38 MAPK), protein kinase B (phospho-AKT), and mammalian target of rapamycin (mTOR).In addition, Mel significantly attenuated the expression of Her-2, p38 MAPK, and p-AKT, which are involved in OC signaling during ethanol intake.Collectively, our results suggest that Mel attenuates the Her-2-signaling pathway in OC of ethanol-preferring rats, providing an effective contribution for further development of adjuvant therapies.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Anatomy, Biosciences Institute, UNESP - Univ. Estadual Paulista, Botucatu-SP, Brazil, 18618-970.

ABSTRACT
Epidermal growth factor receptors 2 (Her-2) and 4 (Her-4) are closely associated with ovarian cancer (OC) progression and metastasis, and a more complete understanding of these signaling pathways allow the development of new therapeutic strategies. Melatonin (Mel) is recognized as having several anticancer properties and has been reported to modulate Her-2 system in aggressive tumors. Here, we investigated OC and the role of Mel therapy on the Her-2- and Her-4-signaling pathway related to downstream molecules in an ethanol-preferring rat model. To induce OC, the left ovary was injected directly with a single dose of 100 µg 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in 10 µL of sesame oil under the bursa. Right ovaries were used as sham-surgery controls. After developing OC, half of the animals received i.p. injections of Mel (200 µg/100 g b.w./day) for 60 days. While Mel therapy was unable to reduce Her-4 and phosphoinositide 3-kinase (PI3K) levels, it was able to suppress the OC-related increase in the levels of the Her-2, p38 mitogen-activated protein kinases (p38 MAPK), protein kinase B (phospho-AKT), and mammalian target of rapamycin (mTOR). In addition, Mel significantly attenuated the expression of Her-2, p38 MAPK, and p-AKT, which are involved in OC signaling during ethanol intake. Collectively, our results suggest that Mel attenuates the Her-2-signaling pathway in OC of ethanol-preferring rats, providing an effective contribution for further development of adjuvant therapies.

No MeSH data available.


Related in: MedlinePlus

Development of OC. (A) Cumulative incidence of OC from 80 to 180 days post-DMBA injection. The combination of EtOH with DMBA showed a significant incidence (%) of tumor development from 140 to 180 days post OC induction. (B) Anatomopathological specimens of OC from 4 week (wk) until 25 wk after tumor induction. Bar = 5 mm, * P < 0.05.
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Figure 1: Development of OC. (A) Cumulative incidence of OC from 80 to 180 days post-DMBA injection. The combination of EtOH with DMBA showed a significant incidence (%) of tumor development from 140 to 180 days post OC induction. (B) Anatomopathological specimens of OC from 4 week (wk) until 25 wk after tumor induction. Bar = 5 mm, * P < 0.05.

Mentions: The combination of EtOH intake with DMBA promoted a high incidence of OC after 140 days of age (Fig. 1A); all differential stages of OC (from 4 to 25 weeks after induction) were recorded during the development (Fig. 1B), and no evidence of altered macroscopic phenotype was observed following EtOH consumption.


Melatonin Attenuates Her-2, p38 MAPK, p-AKT, and mTOR Levels in Ovarian Carcinoma of Ethanol-Preferring Rats.

Ferreira GM, Martinez M, Camargo IC, Domeniconi RF, Martinez FE, Chuffa LG - J Cancer (2014)

Development of OC. (A) Cumulative incidence of OC from 80 to 180 days post-DMBA injection. The combination of EtOH with DMBA showed a significant incidence (%) of tumor development from 140 to 180 days post OC induction. (B) Anatomopathological specimens of OC from 4 week (wk) until 25 wk after tumor induction. Bar = 5 mm, * P < 0.05.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4216796&req=5

Figure 1: Development of OC. (A) Cumulative incidence of OC from 80 to 180 days post-DMBA injection. The combination of EtOH with DMBA showed a significant incidence (%) of tumor development from 140 to 180 days post OC induction. (B) Anatomopathological specimens of OC from 4 week (wk) until 25 wk after tumor induction. Bar = 5 mm, * P < 0.05.
Mentions: The combination of EtOH intake with DMBA promoted a high incidence of OC after 140 days of age (Fig. 1A); all differential stages of OC (from 4 to 25 weeks after induction) were recorded during the development (Fig. 1B), and no evidence of altered macroscopic phenotype was observed following EtOH consumption.

Bottom Line: While Mel therapy was unable to reduce Her-4 and phosphoinositide 3-kinase (PI3K) levels, it was able to suppress the OC-related increase in the levels of the Her-2, p38 mitogen-activated protein kinases (p38 MAPK), protein kinase B (phospho-AKT), and mammalian target of rapamycin (mTOR).In addition, Mel significantly attenuated the expression of Her-2, p38 MAPK, and p-AKT, which are involved in OC signaling during ethanol intake.Collectively, our results suggest that Mel attenuates the Her-2-signaling pathway in OC of ethanol-preferring rats, providing an effective contribution for further development of adjuvant therapies.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Anatomy, Biosciences Institute, UNESP - Univ. Estadual Paulista, Botucatu-SP, Brazil, 18618-970.

ABSTRACT
Epidermal growth factor receptors 2 (Her-2) and 4 (Her-4) are closely associated with ovarian cancer (OC) progression and metastasis, and a more complete understanding of these signaling pathways allow the development of new therapeutic strategies. Melatonin (Mel) is recognized as having several anticancer properties and has been reported to modulate Her-2 system in aggressive tumors. Here, we investigated OC and the role of Mel therapy on the Her-2- and Her-4-signaling pathway related to downstream molecules in an ethanol-preferring rat model. To induce OC, the left ovary was injected directly with a single dose of 100 µg 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in 10 µL of sesame oil under the bursa. Right ovaries were used as sham-surgery controls. After developing OC, half of the animals received i.p. injections of Mel (200 µg/100 g b.w./day) for 60 days. While Mel therapy was unable to reduce Her-4 and phosphoinositide 3-kinase (PI3K) levels, it was able to suppress the OC-related increase in the levels of the Her-2, p38 mitogen-activated protein kinases (p38 MAPK), protein kinase B (phospho-AKT), and mammalian target of rapamycin (mTOR). In addition, Mel significantly attenuated the expression of Her-2, p38 MAPK, and p-AKT, which are involved in OC signaling during ethanol intake. Collectively, our results suggest that Mel attenuates the Her-2-signaling pathway in OC of ethanol-preferring rats, providing an effective contribution for further development of adjuvant therapies.

No MeSH data available.


Related in: MedlinePlus