Abstract
Cancer stem cells are involved in cancer establishment, progression, and resistance to current treatments. We demonstrated the in vitro and in vivo anti-breast cancer effect of bakuchiol in a previous study. However, the ability of bakuchiol to target breast cancer stem cells (BCSCs) and inhibit breast cancer metastasis remains unknown. In the current study, we used the cell surface markers CD44 and CD24 to distinguish BCSCs from MCF-7 cells. Bakuchiol inhibited mammosphere formation and aldehyde dehydrogenase activity in BCSCs. Moreover, bakuchiol induced apoptosis and suppressed the mitochondrial membrane potential of BCSCs. Bakuchiol upregulated the expression levels of pro-apoptotic genes, BNIP3 and DAPK2. Bakuchiol induced oxidative stress and altered lipogenesis in BCSCs. In zebrafish xenografts, bakuchiol inhibited breast cancer cell metastasis in vivo. In addition, bakuchiol altered the expression levels of metastasis-related genes through upregulating CK18 and downregulating Notch3, FASN, TGFBR1, and ACVR1B. Our study provides evidence for the anti-breast cancer potential of bakuchiol.
Highlights
Breast cancer is the second leading cause of cancer death among the women in the United States
Tumorigenesis can be induced in immunodeficient mice through the injection of as few as 200 breast cancer stem cells (BCSCs), which are identified on the basis of the expression of the cell surface makers, such as CD44+/CD24−/low (Al-Hajj et al, 2003)
We found that high-dose bakuchiol inhibited MCF-7 cells in a dose-dependent manner; and we investigated the mechanisms of bakuchiol-induced apoptosis and cell cycle arrest with the doses of 4 and 7 μg/mL in that study (Li et al, 2016)
Summary
Breast cancer is the second leading cause of cancer death among the women in the United States. Both metastases found at diagnosis (de novo) and those occurring later (recurrence) are considered the most severe forms of breast cancer (Mariotto et al, 2017). In vivo, and clinical studies on the effects of phytoestrogen on metastasis have mainly focused on genistein, daidzein, and resveratrol. We demonstrated the in vitro and in vivo inhibitory effect of bakuchiol on breast cancer (Li et al, 2016). The effects of bakuchiol on the growth of BCSCs and breast cancer metastasis have yet to be reported. Prospective results will provide important evidence for the potential of bakuchiol as an anti-breast cancer agent
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