Potential Lead Molecule for the Treatment of Estrogen Positive Breast Cancer
- 詳細技術說明
- We present acetyl plumbagin (AP), a molecule that selectively inhibits ER-positive BC cell growth in vitro as well as in vivo and induces apoptotic cell death by disrupting cholesterol mechanisms, while showing negligible hepatotoxicity and general toxicity in mice.
- *Abstract
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Cholesterol has a vital role in the synthesis of new cell membranes and formation of lipid rafts in which receptors are embedded. Because cancer cells divide more rapidly and overexpress membrane receptors compared to normal cells, they have greater demand for cholesterol in order to sustain proliferation and cell membrane integrity. Cholesterol is also used for the biosynthesis of estrogen which further stimulates growth and proliferation of ERpositive BC. Cholesterol lowering drugs such as statins have been shown to reduce cancer growth in vivo. AP acts as a cholesterol modulator as it disrupts lipid rafts and depletes cholesterol from ERpositive BC cells, resulting in tumor growth inhibition and activation of apoptosis (Fig. A). AP reduces cell viability, disrupts mitochondrial function, activates caspases9 and 7 resulting in PARP1 cleavage, DNA damage and apoptosis.
- 國家/地區
- 美國
