The role of insulin dependent NO synthesis in the impaired production of maspin in human breast cancer

Abstract

The impaired maspin production was found to be the consequence of impaired insulin induced NO production in breast cancer due to the decrease of insulin receptor binding. Restoration of NO production by aspirin can be useful for the restoration of maspin production in breast cancer.

Acetyl salicyclic acid (aspirin) improves synthesis of maspin and lowers incidence of metastasis in breast cancer patients

“…Because the increase of NO synthesis was reported to stimulate maspin synthesis in vitro, (7) we aimed to determine the effect of aspirin therapy in breast cancer patients. It was found that, within 60 min of oral ingestion of aspirin, there was an increase in plasma NO levels and the restoration of impaired plasma maspin levels to normal ranges.…”

“…To determine the effect of aspirin on the synthesis of NO-induced maspin synthesis, neutrophils were prepared from blood of normal volunteers and from the breast cancer subjects at different stages of malignant disease. (8) Typically, neutrophils, reported to synthesize maspin, (7) were isolated from the blood of normal volunteers and breast cancer patients of different stages and the effect of aspirin on the synthesis of maspin was determined by in vitro translation of maspin mRNA, as described in ''Materials and Methods''. It was found that the increase in aspirin concentrations in the assay mixture that resulted in the increased synthesis of NO led to the increased synthesis of maspin (Fig.…”

“…(7) Maspin production in human breast cancer can be restored to normal ranges by using aspirin, which stimulates NO synthesis independently of the insulin receptor both in the case of malignant breast cancer cells in vitro, and in breast cancer patients who ingest the compound orally. (8) This effect of aspirin, resulting in the stimulation of NO synthesis in various cells, has been reported to be independent of the well-known effect of aspirin on the inhibition of prostaglandin synthesis.…”

“…(10) In breast cancer patients, aspirin (given orally) has been reported to result in the restoration of impaired maspin production to normal ranges through the restoration of impaired insulin-induced NO synthesis to normal levels. (7) Based on these results, studies were carried out to determine the effect of chronic ingestion of the compound in patients with breast cancer who had previously received chemotherapy, radiation, and ⁄ or surgery for the localized lesion. Of particular interest was the effect on the occurrence of metastasis by the systemic production of maspin, due to stimulation of NO synthesis by aspirin.…”

The Role of Neutrophil Estrogen Receptor Status on Maspin Synthesis via Nitric Oxide Production in Human Breast Cancer

“…Blood samples (20-25 mL) were collected by venipuncture using siliconized 19-gauge needles in plastic vials, and anticoagulated by gentle mixing of 1 volume of 0.13 M sodium citrate with nine volumes of blood [6]. …”