Abstract
Piperlongumine (PL), a natural product derived from long pepper (Piper longum L.), is known to exhibit anticancer effects. However, the effect of PL on cell cycle-regulatory proteins in estrogen receptor (ER)-positive breast cancer cells is unclear. Therefore, we investigated whether PL can modulate the growth of ER-positive breast cancer cell line, MCF-7. We found that PL decreased MCF-7 cell proliferation and migration. Flow cytometric analysis demonstrated that PL induced G2/M phase cell cycle arrest. Moreover, PL significantly modulated the mRNA levels of cyclins B1 and D1, cyclin-dependent kinases 1, 4, and 6, and proliferating cell nuclear antigen. PL induced intracellular reactive oxygen species (hydrogen peroxide) accumulation and glutathione depletion. PL-mediated inhibition of IKKβ expression decreased nuclear translocation of NF-κB p65. Furthermore, PL significantly increased p21 mRNA levels. In conclusion, our data suggest that PL exerts anticancer effects in ER-positive breast cancer cells by inhibiting cell proliferation and migration via ROS accumulation and IKKβ suppression.
Highlights
Breast cancer is the most frequently diagnosed type of cancer among women
According to a recent report from the World Health Organization (WHO), approximately 0.6 million women died of breast cancer worldwide in 2018, which accounts for 15% of the total cancer-related deaths among women [1]
An nuclear factor-κB (NF-κB) inhibitor (Bay 11-7082), and antibodies against cyclin D1, CDK4, CDK6, proliferating cell nuclear antigen (PCNA), NF-κB p65, IκBα, lamin B, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), goat anti-rabbit IgG-horseradish peroxidase (HRP), and donkey anti-goat IgG-HRP were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA)
Summary
Breast cancer is the most frequently diagnosed type of cancer among women. According to a recent report from the World Health Organization (WHO), approximately 0.6 million women died of breast cancer worldwide in 2018, which accounts for 15% of the total cancer-related deaths among women [1]. Most of the cell growth in breast cancer is mediated by estrogen and the estrogen receptor (ER, e.g., ERα and ERβ) [2]. ER can deliver signals into the nucleus via regulation of transcription factors, including activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) [3,4]. Two-thirds of the breast cancers are ER-positive; in these cancers, cell growth and proliferation are dependent on the presence of estrogen [5]. A breast cancer cell line, MCF-7, which is ER-positive, was employed in this study
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