Limits...
Meroxest improves the prognosis of immunocompetent C57BL/6 mice with allografts of E0771 mouse breast tumor cells

View Article: PubMed Central - PubMed

ABSTRACT

Introduction: Recently, we have reported the antitumor properties of a new family of synthetic merosesquiterpenes, among which meroxest is highlighted, since it has high activity and specificity for ER+ breast cancer cells. In this paper, we characterize allografts of ER+ E0771 mouse breast tumor cells in immunocompetent C57BL/6 mice, and also analyze the effect of meroxest on the prognosis of the disease.

Material and methods: Twenty female C57BL/6 mice were injected with 106 E0771 cells. Once the tumors reached the appropriate size, the mice were divided into two groups, one control and another treated orally with 15 mg/kg of meroxest. After 20 days, tumor samples were taken for histopathological study and for determination of the expression of the prognostic markers Ki67 and vascular endothelial growth factor (VEGF) by immunofluorescence.

Results: In sections stained with hematoxylin-eosin, we observed that tumors have a well-defined capsule enclosing E0771 tumor cells. The central area of tumors contains necrotic regions with leukocyte infiltration. Meroxest treatment significantly reduces tumor size (68%, p < 0.05), induces changes in its structure, decreases the degree of leukocyte infiltration, and significantly reduces the expression of Ki67 (33%, p < 0.05) and VEGF (82%, p < 0.05).

Conclusions: Meroxest improves the prognosis of mice since it reduces leukocyte infiltration, and decreases the expression of Ki67 and VEGF markers. Consequently, the merosesquiterpene could become a useful antiangiogenic drug in the treatment of breast cancer. These results encourage us to deepen the study of meroxest, in order to find more evidence that supports the convenience of its evaluation in a clinical study or trial.

No MeSH data available.


Chemical structure of meroxest
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5016567&req=5

Figure 0001: Chemical structure of meroxest

Mentions: We have recently reported the antitumor properties of a new family of synthetic merosesquiterpenes. These compounds, whose synthesis and effects are protected under international patents WO/2009/112622 and WO/2010/076358, have cytotoxic activity against human breast, colon, and lung tumor cells. However, they have shown greater specificity against breast cells. Among them, compound 13 was highlighted, henceforth referred to as meroxest (Figure 1). It has elevated activity and specificity against the luminal breast cancer cell MCF-7. We proved that potent antitumor activity of meroxest against MCF-7 was mediated by the induction of oxidative stress; cell cycle arrest in G0–G1 phase accompanied by downregulation of cyclin D1, pRb hypophosphorylation and increased expression of p27; and apoptosis associated with increased expression of p53 and poly (ADP-ribose) polymerase (PARP) fractioning. Moreover, meroxest appears to inhibit epithelial-mesenchymal transition, a process involved in metastasis and associated with poor prognosis. The in vitro results prompted us to assess its effect in vivo. For this purpose, we analyzed the effect of meroxest on tumor growth in immunocompetent C57BL/6 mice with allografts of E0771 mouse breast tumor cells (luminal subtype), and we found that meroxest markedly reduced the volume of tumors [22].


Meroxest improves the prognosis of immunocompetent C57BL/6 mice with allografts of E0771 mouse breast tumor cells
Chemical structure of meroxest
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5016567&req=5

Figure 0001: Chemical structure of meroxest
Mentions: We have recently reported the antitumor properties of a new family of synthetic merosesquiterpenes. These compounds, whose synthesis and effects are protected under international patents WO/2009/112622 and WO/2010/076358, have cytotoxic activity against human breast, colon, and lung tumor cells. However, they have shown greater specificity against breast cells. Among them, compound 13 was highlighted, henceforth referred to as meroxest (Figure 1). It has elevated activity and specificity against the luminal breast cancer cell MCF-7. We proved that potent antitumor activity of meroxest against MCF-7 was mediated by the induction of oxidative stress; cell cycle arrest in G0–G1 phase accompanied by downregulation of cyclin D1, pRb hypophosphorylation and increased expression of p27; and apoptosis associated with increased expression of p53 and poly (ADP-ribose) polymerase (PARP) fractioning. Moreover, meroxest appears to inhibit epithelial-mesenchymal transition, a process involved in metastasis and associated with poor prognosis. The in vitro results prompted us to assess its effect in vivo. For this purpose, we analyzed the effect of meroxest on tumor growth in immunocompetent C57BL/6 mice with allografts of E0771 mouse breast tumor cells (luminal subtype), and we found that meroxest markedly reduced the volume of tumors [22].

View Article: PubMed Central - PubMed

ABSTRACT

Introduction: Recently, we have reported the antitumor properties of a new family of synthetic merosesquiterpenes, among which meroxest is highlighted, since it has high activity and specificity for ER+ breast cancer cells. In this paper, we characterize allografts of ER+ E0771 mouse breast tumor cells in immunocompetent C57BL/6 mice, and also analyze the effect of meroxest on the prognosis of the disease.

Material and methods: Twenty female C57BL/6 mice were injected with 106 E0771 cells. Once the tumors reached the appropriate size, the mice were divided into two groups, one control and another treated orally with 15 mg/kg of meroxest. After 20 days, tumor samples were taken for histopathological study and for determination of the expression of the prognostic markers Ki67 and vascular endothelial growth factor (VEGF) by immunofluorescence.

Results: In sections stained with hematoxylin-eosin, we observed that tumors have a well-defined capsule enclosing E0771 tumor cells. The central area of tumors contains necrotic regions with leukocyte infiltration. Meroxest treatment significantly reduces tumor size (68%, p < 0.05), induces changes in its structure, decreases the degree of leukocyte infiltration, and significantly reduces the expression of Ki67 (33%, p < 0.05) and VEGF (82%, p < 0.05).

Conclusions: Meroxest improves the prognosis of mice since it reduces leukocyte infiltration, and decreases the expression of Ki67 and VEGF markers. Consequently, the merosesquiterpene could become a useful antiangiogenic drug in the treatment of breast cancer. These results encourage us to deepen the study of meroxest, in order to find more evidence that supports the convenience of its evaluation in a clinical study or trial.

No MeSH data available.