Roles of JNK/Nrf2 Pathway on Hemin-Induced Heme Oxygenase-1 Activation in MCF-7 Human Breast Cancer Cells

• Published in: Medicina (Kaunas, Lithuania) Lithuania), 2020-05, Vol.56 (6), p.268
• Main Authors: Jang, Hye-Yeon, Hong, On-Yu, Chung, Eun-Yong, Park, Kwang-Hyun, Kim, Jong-Suk
• Format: Article
• Language: English
• Subjects: Benzopyrans - pharmacology; breast cancer; Breast Neoplasms - pathology; Cells, Cultured - drug effects; Cells, Cultured - pathology; Communication; heme oxygenase-1; Heme Oxygenase-1 - drug effects; hemin; Hemin - pharmacology; Humans; JNK; MAP Kinase Signaling System - drug effects; MCF-7; MCF-7 Cells - drug effects; NF-E2-Related Factor 2 - pharmacology; NF-E2-Related Factor 2 - therapeutic use; Nrf2
• ISSN: 1648-9144; 1010-660X; 1648-9144
• DOI: 10.3390/medicina56060268

Heme oxygenase-1 (HO-1) is highly induced in various human disease states, including cancer, indicating that HO-1 is an emerging target of cancer therapy. In this study, we investigated that the mechanisms of hemin-induced HO-1 expression and its signaling pathways in human breast cancer cell. We used MCF-7 cells, a human breast cancer cell line. Hemin increased HO-1 expression in MCF-7 cells in a dose- and time-dependent manner. Hemin enhanced HO-1 expression through the activation of c-Jun N-terminal kinases (JNK) signaling pathway. Hemin also induced activation of Nrf2, a major transcription factor of HO-1 expression. These responses in MCF-7 cells were completely blocked by pretreatment with brazilin, a HO-1 regulator. These results indicated that brazilin inhibits hemin-induced HO-1 expressions through inactivation of JNK/Nrf2 in MCF-7 cells. Thus, our findings suggest that HO-1 is an important anticancer-target of brazilin in human breast cancer.