- 作者: Yu-Wen Chu, Shu-Ting Liu, Ya-Lan Yang, Shih-Ming Huang and Wei-Ming Wang
- 作者服務機構: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan, Republic of China
- 中文摘要:
- 英文摘要:
Background
Epigallocatechin gallate (EGCG) is the major ingredient of sinecatechins ointment, approved for the treatment of external genital and perianal warts. However, the molecular mechanism for EGCG’s effect on warts resulting from the human papillomavirus (HPV) infection of keratinocytes is not well understood. HPV may survive in proliferative keratinocytes and may be involved in cell cycle regulation and progression. The objective of this study was to investigate the mechanism underlying EGCG’s treatment on external genital warts of HPV infection through the cultured keratinocyte cells from the HaCaT cell line.
Methods
MTT and flow cytometry assays were used to measure cell viability and the cell cycle profile, with and without EGCG treatment, for HaCaT keratinocyte cells cultured in a calcium-free medium and 1.8 mM calcium which induced proliferative and differentiated keratinocytes, respectively, for 24 h. The expression levels of cytotoxic proteins and factors were evaluated with the RT-PCR and western blotting analysis.
Results
EGCG influenced the proliferation stage but not the differentiation stage of keratinocytes. We suggest that apoptosis and autophagy might be the possible mechanism for the EGCG’s effect on the proliferative HaCaT cells. Furthermore, we found that EGCG reduced the protein levels of cyclin D1 and Zac1 (a zinc-finger protein which regulates apoptosis and cell cycle arrest 1) dose-dependently in proliferative as compared to differentiated keratinocytes. It also induced the expression of p21 and DEC1 (differentiated embryo-chondrocyte expressed gene 1), and promoted G1 arrest of cell cycle in proliferative keratinocytes.
Conclusions
These results help clarify the mechanisms of EGCG treatment of HPV-infected keratinocytes and may contribute to new targets, such as Zac1 and DEC1 for external genital and perianal warts. - 中文關鍵字:
- 英文關鍵字: Epigallocatechin-3-gallate, Keratinocytes, Proliferation, HPV, External genital warts