Enhancement of UVB-induced apoptosis by apigenin in human keratinocytes and organotypic keratinocyte cultures

被引:46
|
作者
Abu-Yousif, Adrian O. [1 ,3 ,5 ]
Smith, Kimberly A. [1 ,5 ]
Getsios, Spiro [2 ]
Green, Kathleen J. [1 ,2 ]
Van Dross, Rukiyah T. [4 ]
Pelling, Jill C. [1 ,5 ]
机构
[1] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA
[2] Northwestern Univ, Feinberg Sch Med, Dept Dermatol, Chicago, IL 60611 USA
[3] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA
[4] E Carolina Univ, Brody Sch Med, Dept Pharmacol & Toxicol, Greenville, NC USA
[5] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
关键词
D O I
10.1158/0008-5472.CAN-07-2763
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Topical application of the bioflavonoid 4',5,7-trihydroxyflavone (apigenin) to mouse skin effectively reduces the incidence and size of skin tumors caused by UVB exposure. The ability to act as a chemopreventive compound indicates that apigenin treatment alters the molecular events initiated by UVB exposure; however, the effects of apigenin treatment on UVB-irradiated keratinocytes are not fully understood. In the present study, we have used three models of human keratinocytes to study the effect of apigenin treatment on UVB-induced apoptosis: HaCaT human keratinocyte cells, primary keratinocyte cultures isolated from human neonatal foreskin, and human organotypic keratinocyte cultures. Each keratinocyte model was exposed to a moderate dose of UVB (300-1,000 J/m(2)), then treated with apigenin (0-50 mu mol/L), and harvested to assess apoptosis by Western blot analysis for poly(ADP)ribose polymerase cleavage, annexin-V staining by flow cytometry, and/or the presence of sunburn cells. Apigenin treatment enhanced UVB-induced apoptosis > 2-fold in each of the models tested. When keratinocytes were exposed to UVB, apigenin treatment stimulated changes in Bax localization and increased the release of cytochrome c from the mitochondria. compared with UVB exposure alone. Overexpression of the antiapoptotic protein Bcl-2 and expression of a dominant-negative form of Fas-associated death domain led to a reduction in the ability of apigenin to enhance UVB-induced apoptosis. These results suggest that enhancement of UVB-induced apoptosis by apigenin treatment involves both the intrinsic and extrinsic apoptotic pathways. The ability of apigenin to enhance UVB-induced apoptosis may explain, in part, the photochemopreventive effects of apigenin.
引用
收藏
页码:3057 / 3065
页数:9
相关论文
共 50 条
  • [21] Galectin-3 protects keratinocytes from UVB-induced apoptosis
    Saegusa, J.
    Hsu, D. K.
    Kuwabara, I.
    Liu, W.
    Kuwabara, Y.
    Yu, L.
    Liu, F.
    JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2006, 126 : 131 - 131
  • [22] Withdrawal of growth factors causes increased susceptibility to UVB-induced apoptosis in human keratinocytes.
    Kuhn, C
    Kumar, M
    Hurwitz, S
    Cotton, J
    Spandau, DF
    JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1997, 108 (04) : 407 - 407
  • [23] Role of p53 in UVB-induced apoptosis in HaCaT keratinocytes
    Henseleit, U
    Zhang, J
    Wanner, R
    Kolde, G
    Rosenbach, T
    JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1996, 106 (04) : 420 - 420
  • [24] Alkannin, HSP70 Inducer, Protects against UVB-Induced Apoptosis in Human Keratinocytes
    Yoshihisa, Yoko
    Hassan, Mariame Ali
    Furusawa, Yukihiro
    Tabuchi, Yoshiaki
    Kondo, Takashi
    Shimizu, Tadamichi
    PLOS ONE, 2012, 7 (10):
  • [25] BMAL1 and CLOCK proteins in regulating the sensitivity of human keratinocytes to UVB-induced apoptosis
    Sun, Y.
    Wang, P.
    Dai, J.
    JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2018, 138 (05) : S197 - S197
  • [26] Effect of N-acetylcysteine on UVB-induced apoptosis and DNA repair in human and mouse keratinocytes
    Bush, JA
    Ho, VC
    Mitchell, DL
    Tron, VA
    Li, G
    PHOTOCHEMISTRY AND PHOTOBIOLOGY, 1999, 70 (03) : 329 - 333
  • [27] Enhancement of Protective Effects of Radix Scutellariae on UVB-induced Photo Damage in Human HaCaT Keratinocytes
    Wang, Yu-shuai
    Cho, Jin-Gyeong
    Hwang, Eun-Son
    Yang, Jung-Eun
    Gao, Wei
    Fang, Min-zhe
    Zheng, Sheng-dao
    Yi, Tae-Hoo
    APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY, 2018, 184 (04) : 1073 - 1093
  • [28] Enhancement of Protective Effects of Radix Scutellariae on UVB-induced Photo Damage in Human HaCaT Keratinocytes
    Yu-shuai Wang
    Jin-Gyeong Cho
    Eun-Son Hwang
    Jung-Eun Yang
    Wei Gao
    Min-zhe Fang
    Sheng-dao Zheng
    Tae-Hoo Yi
    Applied Biochemistry and Biotechnology, 2018, 184 : 1073 - 1093
  • [29] Possible involvement of Hsp27 oligomerization in UVB-induced apoptosis of keratinocyte
    Choi, D.
    Sohn, K.
    Kwon, Y.
    Kim, N.
    Cho, A.
    Lee, Y.
    Yoon, T.
    Lee, Y.
    Kim, C.
    Lee, J.
    JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2009, 129 : S128 - S128
  • [30] Quantitative analysis of UVB-induced apoptosis in human epidermis
    Hurwitz, SA
    Spandau, DF
    EXPERIMENTAL DERMATOLOGY, 2000, 9 (03) : 185 - 191