Sudachitin, a polymethoxyflavone from Citrus sudachi, induces apoptosis via the regulation of MAPK pathways in human keratinocyte HaCaT cells

• Published in: Biochemical and biophysical research communications 2019-11, Vol.519 (2), p.344-350
• Main Authors: Abe, Shogo, Yuasa, Keizo
• Format: Article
• Language: English
• Subjects: Apoptosis; Cell migration and proliferation; Keratinocyte; MAPK; Polymethoxyflavone
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.09.010

Although we recently reported that sudachitin (5,7,4′-trihydroxy-6,8,3′-trimethoxyflavone), a polymethoxyflavone isolated from the peel of Citrus sudachi, can induce apoptosis in human keratinocyte HaCaT cells, the mechanism underlying its action remains unclear. In this study, we explored the mechanisms underlying sudachitin-induced apoptosis in HaCaT cells. Sudachitin activated p38MAPK and inhibited ERK1/2, whereas another polymethoxyflavone, nobiletin (5,6,7,8,3′,4′-hexamethoxyflavone), activated ERK1/2. The p38MAPK inhibitor SB203580 significantly attenuated sudachitin-induced heat shock protein 27 phosphorylation, downstream of p38MAPK, and subsequent apoptosis, indicating that sudachitin induces apoptosis via the p38MAPK pathway. Additionally, sudachitin inhibited serum- and EGF-stimulated Raf-1-ERK1/2 activation, and blocked EGF-induced cell migration and proliferation in HaCaT cells. These results suggest that small structural differences in polymethoxyflavones can induce different cellular responses by altering the regulation of MAPK activities and that sudachitin may be a potential candidate for developing new drugs for skin diseases such as psoriasis. [Display omitted] •Sudachitin induces apoptosis through the regulation of MAPK pathways in keratinocytes.•Sudachitin activates the p38MAPK pathway, while nobiletin activates the ERK1/2 pathway.•Sudachitin inhibits serum- and EGF-stimulated ERK1/2 activation in keratinocytes.•Sudachitin suppresses EGF-induced migration and proliferation of keratinocytes.