Targeting breast stem cells with the cancer preventive compounds curcumin and piperine.
Breast Cancer Res Treat. 2010;122(3):777-85
According to the cancer stem cell hypothesis, malignancies arise in tissue stem and/or progenitor cells through the dysregulation or acquisition of self-renewal. While differentiated cells turn over rapidly, stem cells are long lived and capable of acquiring multiple mutations over time to transform to malignancy. Hence, it has been hypothesized that dysregulated self-renewal leading to clonal expansion of stem cell populations could be the first step in the progression of carcinogenesis.
Thus, strategies aimed at targeting stem cell self-renewal pathways represent rational approaches for cancer prevention. Wnt is one such signaling pathway that plays a major role in several types of malignancies, including breast cancer.
Curcumin has been found to downregulate the Wnt signaling pathway and there are substantial evidence in preclinical models showing that Curcumin is a potent chemopreventive dietary agent. Similarly, Piperine has also been suggested to be effective against cancer incidence in chemical rodent models of lung cancer and it also well known to enhance the bioavailability of Curcumin if these chemopreventive agents are given in combination.
To determine whether Curcumin and Piperine modulate the self-renewal of normal and malignant breast stem cells.
Effect of Curcumin and Piperine alone and/or in combination on mammosphere formation, expression of the breast stem cell marker aldehyde dehydrogenase (ALDH) and Wnt signaling was determined.
- Curcumin at 5 μM and 10 μM inhibited mammosphere formation by 50% and 100% compared to controls. Combination of Piperine (10 μM) and Curcumin (5 μM) further reduced mammosphere formation compared to either agent separately
- Combination of Curcumin (5 μM) and Piperine (10 μM) decreased stem cell self-renewal by more than 50% compared to DMSO control
- Curcumin (5 μM) and Piperine (5 μM) affect ALDH+ stem/progenitor cells by inhibiting mammosphere formation by 50% compared to DMSO control
- Both Curcumin (10 μM) and Piperine (10 μM) reduced the percent of cells expressing the stem cell marker ALDH1 alone as well as in combination
- Combination of Curcumin (10 μM) and Piperine (10 μM) showed the potent inhibitory effect on Wnt signaling
Curcumin and Piperine separately, and in combination, inhibited breast stem cell self-renewal but with no toxicity to differentiated cells. Hence, these compounds could be potential cancer preventive agents.