br Corresponding authors br E mail addresses Zhangfengxue gz
E-mail addresses: [email protected] (F. Zhang), [email protected] (H. Wang).
1 Co first author, contributed equally.
(Siegel et al., 2018). Breast cancer remains the most prevalent and fatal malignant tumor and also the primary reason for cancer-related death in women, especially in white women worldwide (Desantis et al., 2016). Moreover, the increase in breast cancer incidence between 2005 and 2014 was reported to be by 1.7% per year among Asian women (Desantis et al., 2017). Current clinical cancer treatments including surgical therapy, radiotherapy, chemotherapy and biotherapy are used to treat breast cancer. Progress has been made in reducing or removing primary tumor sites in the past several decades. However, relapse and metastasis, which are the main causes of breast cancer-related death, are severely intractable in the clinic and remain poorly understood (Lu et al., 2009).
Breast cancer metastasis occurs when cancer cells migrate from their primary location to a new site or to different organs such as the lungs, bones, or the brain. One of the possible mechanisms of cancer metastasis is that cancer cells break off from their original tumor and enter the blood and lymphatic systems. Some of the metastatic cancer cells can escape the host's immunosurveillance system and be carried by the bloodstream or lymphatic fluid to new sites in the body (Hu et al., 2015). It is more challenging when breast cancer cells migrate and metastasize as these processes are associated with poor survival and prognosis. Preventing cancer metastasis and treating cancer once me-tastasized are critically important in both cancer research and clinical practices.
Cancer stem cells (CSCs), like normal stem cells, have self-renewal abilities and differentiate into various different cancer cells that drive tumorigenesis and growth. These only account for a small portion of the cancer cell population, but importantly, CSCs function as tumor-in-itiating cells in many types of tumors, including acute myeloid leu-kemia (AML), breast cancer, Anidulafungin tumors, colon cancer, pancreatic cancer, lung cancer and liver cancer (Mackillop et al., 1983; Bonnet et al., 1997; Alhajj et al., 2003; Ponti et al., 2005; Singh et al., 2004; O'Brien et al., 2007; Li et al., 2007; Eramo et al., 2008; Yang et al., 2008). CSCs have self-renewal capabilities and are multipotent, thus they may contribute to therapy resistance, subsequently leading to disease progression and relapse (Vlashi et al., 2011; Lagadec et al., 2010). CSCs also exhibit decreased adhesion and increased motility. They play pivotal roles in cancer cell invasion and metastasis via in-teractions with epithelial-mesenchymal transition (EMT) (Weng et al., 2012; Lawson et al., 2009; Liu et al., 2010; Jang et al., 2015; Ma et al., 2014; Mani et al., 2008; Morel et al., 2008; Guttilla et al., 2012).
In 2003, Alhajj et al. (2003) isolated a small number of breast cancer stem-like cells (BCSCs) from the breast tumor bulk with anti-genic phenotype CD44+CD24−/low, confirming that BCSCs also exist in breast cancer for the first time. They revealed that these cells with CD44+CD24−/low surface markers were highly enriched for stem-like cells when compared with the majority of cancer cells with the CD44lowCD24+ phenotype found in the same breast tumors (Alhajj et al., 2003). Since then, mammosphere culture with serum free medium (SFM) has been widely used for the enrichment of mammary epithelial stem cells and BCSCs (Cariati et al., 2008; Phillips et al., 2006; Croker and Allan, 2012; Leis et al., 2011; Cui et al., 2016). Given the importance of CSCs and EMT in tumor initiation, invasion, and me-tastasis, novel therapeutic strategies and new drugs targeting both EMT and CSCs in breast cancer have become important to improve the sur-vival and quality of lives of patients with cancer, especially those al-ready diagnosed with cancer metastasis.
Curcumin is the main curcuminoid extracted from the rhizome of Curcuma longa. It has been widely used in clinics for the treatment and prevention of various inflammatory diseases and cancer. In addition, many pharmacological activities of curcumin have been reported, in-cluding anti-oxidant (Dinkova-Kostova et al., 2008), anti-inflammatory (Pulido-Moran et al., 2016), cancer chemoprevention (Kotecha et al., 2016) and anti-cancer activities (López-Lázaro et al., 2008). Given the accumulating evidence indicating that curcumin inhibits cancer cell proliferation and tumor growth in animal models (Kotecha et al., 2016; Phytomedicine 58 (2019) 152740
López-Lázaro et al., 2008), further studies investigating the underlying mechanism are required as well as translational studies.