The Role of Breastmilk in Macrophage-Tumour Cell Interactions in Postpartum Breast Cancer.

Background: Lactation is associated with long-term reduced risk of breast cancer. However, there is a transient increased risk of breast cancer in the 5 to 10 years postpartum and this is associated with a high incidence of metastasis and mortality. Breastmilk is a physiological fluid secreted by the mammary glands intimately connected with breast cells and the microenvironment that may affect postpartum breast cancer development and progression.

Synthesis of steroidal inhibitors for Mycobacterium tuberculosis.

Oxidised derivatives of cholesterol have been shown to inhibit the growth of Mycobacterium tuberculosis (Mtb). The bacteriostatic activity of these compounds has been attributed to their inhibition of CYP125A1 and CYP142A1, two metabolically critical cytochromes P450 that initiate degradation of the sterol side chain. Here, we synthesise and characterise an extensive library of 28 cholesterol derivatives to develop a structure-activity relationship for this class of inhibitors.

The oxidation of steroid derivatives by the CYP125A6 and CYP125A7 enzymes from Mycobacterium marinum.

The members of the bacterial cytochrome P450 (CYP) monooxygenase family CYP125, catalyze the oxidation of steroid derivatives including cholesterol and phytosterols, as the initial activating step in their catabolism. However, several bacterial species contain multiple genes encoding CYP125 enzymes and other CYP enzymes which catalyze cholesterol/cholest-4-en-3-one hydroxylation. An important question is why these bacterium have more than one enzyme with overlapping substrate ranges capable of catalyzing the terminal oxidation of the alkyl chain of these sterols.

The bacterial cytochrome P450 (CYP) CYP125 enzymes can competitively oxidise sitosterol in the presence of cholesterol.

Cholesterol catabolism is an important survival mechanism for the pathogenic . Various other mycobacteria degrade not only cholesterol but plant sterols such as sitosterol and campesterol. In this work we demonstrate that the cytochrome P450 (CYP) CYP125 enzyme family is capable of sitosterol and campesterol side-chain oxidation and activation in these bacteria.

The oxidation of cholesterol derivatives by the CYP124 and CYP142 enzymes from Mycobacterium marinum.

The CYP124 and CYP142 families of bacterial cytochrome P450 monooxygenases (CYPs), catalyze the oxidation of methyl branched lipids, including cholesterol, as one of the initial activating steps in their catabolism. Both enzymes are reported to supplement the CYP125 family of P450 enzymes. These CYP125 enzymes are found in the same bacteria, and are the primary cholesterol/cholest-4-en-3-one metabolizing enzymes.