文摘
We have previously reported that high aldehyde dehydrogenase (ALDH) enzyme activity in breast cancer cells results in breast cancer stem cell (BCSC) properties by upregualting Notch-1 and epithelial mesenchymal markers. This results in chemoresistance in breast cancer. Here, we examined the functional and clinical significance of ALDH expression by measuring the ALDH levels in breast cancer tissues by immunohistochemistry. There was a significantly higher ALDH expression in higher grade breast cancer tumor tissues (Grade- II and III) versus normal breast tissues. Injection of BCSC (ALDHp>+p> and CD44p>+p>/CD22p>−p>) cells resulted in aggressive tumor growth in athymic mice versus ALDHp>−p> cells. The ALDHp>+p> and CD44p>+p>/CD22p>−p> tumors grow rapidly and are larger than ALDHp>−p> tumors which were slow growing and smaller. Molecularly, ALDHp>+p> tumors expressed higher expression of Notch-1 and EMT markers than ALDHp>−p> tumors. Oral administration of the naturally occurring Psoralidin (Pso, 25 mg/kg of body weight) significantly inhibited the growth in ALDHp>+p> and ALDHp>−p> tumors as well. Psoralidin inhibited Notch-1 mediated EMT activation in ALDHp>+p> and ALDHp>−p> tumors-this confirms our in vitro findings. Our results suggest that Notch-1 could be an attractive target and inhibition of Notch-1 by Psoralidin may prevent pathogenesis of breast cancer as well as metastasis.