Gupta Sanjay, Afaq Farrukh, Mukhtar Hasan
Department of Dermatology, Case Western Reserve University & The Research Institute of University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, Ohio 44106, USA.
Oncogene. 2002 May 23;21(23):3727-38. doi: 10.1038/sj.onc.1205474.
Apigenin, a common dietary flavonoid abundantly present in fruits and vegetables, may have the potential for prevention and therapy for prostate cancer. Here, we report for the first time that apigenin inhibits the growth of androgen-responsive human prostate carcinoma LNCaP cells and provide molecular understanding of this effect. The cell growth inhibition achieved by apigenin treatment resulted in a significant decrease in AR protein expression along with a decrease in intracellular and secreted forms of PSA. These effects were also observed in DHT-stimulated cells. Further, apigenin treatment of LNCaP cells resulted in G1 arrest in cell cycle progression which was associated with a marked decrease in the protein expression of cyclin D1, D2 and E and their activating partner cdk2, 4 and 6 with concomitant induction of WAF1/p21 and KIP1/p27. The induction of WAF1/p21 appears to be transcriptionally upregulated and is p53 dependent. In addition, apigenin inhibited the hyperphosphorylation of the pRb protein in these cells. Apigenin treatment also resulted in induction of apoptosis as determined by DNA fragmentation, PARP cleavage, fluorescence microscopy and flow cytometry. These effects were found to correlate with a shift in Bax/Bcl-2 ratio more towards apoptosis. Apigenin treatment also resulted in down-modulation of the constitutive expression of NF-kappaB/p65. Taken together, these findings suggest that apigenin has strong potential for development as an agent for prevention against prostate cancer.
芹菜素是一种常见的膳食类黄酮，大量存在于水果和蔬菜中，可能具有预防和治疗前列腺癌的潜力。在此，我们首次报道芹菜素可抑制雄激素反应性人前列腺癌LNCaP细胞的生长，并对这种作用进行分子层面的解读。芹菜素处理所实现的细胞生长抑制导致AR蛋白表达显著降低，同时细胞内和分泌形式的PSA也减少。在双氢睾酮刺激的细胞中也观察到了这些效应。此外，用芹菜素处理LNCaP细胞导致细胞周期进程停滞于G1期，这与细胞周期蛋白D1、D2和E及其激活伴侣细胞周期蛋白依赖性激酶2、4和6的蛋白表达显著降低相关，同时伴随WAF1/p21和KIP1/p27的诱导。WAF1/p21的诱导似乎是转录上调的，且依赖于p53。此外，芹菜素抑制了这些细胞中pRb蛋白的过度磷酸化。通过DNA片段化、PARP裂解、荧光显微镜和流式细胞术检测发现，芹菜素处理还导致了细胞凋亡的诱导。这些效应与Bax/Bcl-2比值向凋亡方向的转变相关。芹菜素处理还导致NF-κB/p65组成型表达的下调。综上所述，这些发现表明芹菜素作为一种预防前列腺癌的药物具有很强的开发潜力。
