Study on Lycopene Regulates Stemness and Chemosensitivity of Breast Cancer Stem Cell Through ROS/NF-κB Signaling

OBJECTIVE To investigate the effect of lycopene on the stemness and chemotherapy sensitivity of breast cancer stem cells(BCSC) and its possible mechanism. METHODS Breast cancer cells MCF-7 were cultured in vitro, CD44⁺ MCF-7 stem cells(BCSC) were screened by suspension culture and flow cytometry for follow-up experiments. BCSC were divided into control group and lycopene group(5 μmol·L^–1). After administration for 24 h, sphere formation assay was used to detect the size and number of spheroid BCSC cells. BCSC in control group and lycopene group were treated cisplatin at different concentrations(0, 5, 10, 20, 40 and 80 μmol·L^–1) for 24 h. CCK8 assay was used to detect BCSC cell proliferation and flow cytometry was used to detect apoptosis. Reactive oxygen species(ROS) levels were detected by flow cytometry in BCSC of control group and lycopene group. BCSC were treated with 10 μmol·L–1 N-acetyl-L-cysteine(NAC) or 10 μmol·L^–1 BAY11-7085 (BAY) for 24 h. Western blotting was used to detect the protein expression of p NF-κB and stemness-related proteins LSD1 and SOX9. RESULTS The protein expression levels of LSD1 and SOX9 in CD44⁺ cells were significantly higher than those in CD44^- cells. Lycopene significantly reduced the number and size of BCSC spheres. Lycopene significantly increased the apoptosis rate of BCSC cells induced by cisplatin. Furthermore, lycopene significantly reduced ROS levels in BCSC. Lycopene and NAC both reduced the expression level of p NF-κB protein in BCSC cells. Importantly, lycopene, NAC and BAY all inhibited the expression levels of LSD1 and SOX9 proteins in cells, and all increased the sensitivity to cisplatin of BCSC. CONCLUSION Lycopene may inhibit the stemness and enhance the sensitivity to cisplatin of breast cancer stem cells through the ROS/NF-κB signaling pathway.