Dujic Jadranka, Kippenberger Stefan, Ramirez-Bosca Ana, Diaz-Alperi Joaquin, Bereiter-Hahn Jürgen, Kaufmann Roland, Bernd August, Hofmann Matthias
Department of Dermatology and Venerology, JW Goethe-University, Medical School, Frankfurt, Main, Germany.
Int J Cancer. 2009 Mar 15;124(6):1422-8. doi: 10.1002/ijc.23997.
It is known that curcumin, a dietary pigment from the plant Curcuma longa, inhibits cell proliferation and induces apoptosis in different cell lines; however, the therapeutic benefit is hampered by very low absorption after transdermal or oral application. Recent studies from our laboratory have demonstrated that curcumin at low concentrations (0.2-1 microg/ml) offered the described effects only when applied with UVA or visible light. Nevertheless, the in vivo efficacy of this combination is lacking. In the present study, we used a xenograft tumor model with human epithelial carcinoma A431 cells to test the effect of curcumin and visible light on tumor growth. It was found that tumor growth was significantly inhibited in mice that were i.p. injected with curcumin and consecutively irradiated with visible light. Furthermore, immunohistochemistry showed a reduction of Ki 67 expression, indicating a decrease of cycling cells and induction of apoptotic bodies. The effect on apoptosis was further confirmed by Western blot analysis showing enhanced activation of caspases-9. Vice versa inhibition of extracellular regulated kinases (ERK) 1/2 and epidermal growth factor receptor (EGF-R) was observed which may aid inhibition of proliferation and induction of apoptosis. In summary, the present findings suggest a combination of curcumin and light as a new therapeutic concept to increase the efficacy of curcumin in the treatment of cancer.
已知姜黄素是一种从植物姜黄中提取的食用色素,可抑制不同细胞系的细胞增殖并诱导其凋亡;然而,经皮或口服应用后其吸收极低,这限制了其治疗效果。我们实验室最近的研究表明,低浓度(0.2 - 1微克/毫升)的姜黄素仅在与紫外线A(UVA)或可见光联合应用时才具有上述作用。然而,这种联合应用的体内疗效尚缺乏研究。在本研究中,我们使用人上皮癌A431细胞的异种移植肿瘤模型来测试姜黄素和可见光对肿瘤生长的影响。结果发现,腹腔注射姜黄素并连续照射可见光的小鼠肿瘤生长受到显著抑制。此外,免疫组织化学显示Ki 67表达降低,表明循环细胞减少并诱导凋亡小体形成。蛋白质免疫印迹分析显示半胱天冬酶-9的激活增强,进一步证实了对凋亡的影响。反之,观察到细胞外调节激酶(ERK)1/2和表皮生长因子受体(EGF-R)受到抑制,这可能有助于抑制增殖和诱导凋亡。总之,本研究结果提示姜黄素与光联合应用是一种提高姜黄素治疗癌症疗效的新治疗理念。