Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
Anticancer Res. 2012 Sep;32(9):3689-98.
Previous studies suggested chalcones as antineoplastic drug candidates. We synthesized a new chalcone derivative (E)-3-(4-methoxyphenyl)-2-methyl-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one, (CHO27) with an up to 1000-fold increased cytotoxic potency relative to its parent compound in cell culture assays. CHO27 at low nanomolar levels, inhibited prostate cancer (PCa) cell growth through cell cycle arrest and caspase-dependent apoptosis. Activation of p53 accounted for, at least in part, the growth inhibition by CHO27 in vitro. Furthermore, i.p. administration of CHO27 suppressed the growth of established PCa 22Rv1 xenograft tumors accompanied with p53 and p21(Cip1) induction. CHO27 may be a lead for development of new therapeutic agents for PCa.
先前的研究表明查耳酮是一种具有抗肿瘤活性的药物候选物。我们合成了一种新的查尔酮衍生物（E）-3-（4-甲氧基苯基）-2-甲基-1-（3,4,5-三甲氧基苯基）-2-丙烯-1-酮（CHO27），其在细胞培养实验中的细胞毒性比其母体化合物高 1000 倍。CHO27 在低纳摩尔水平时通过细胞周期阻滞和 caspase 依赖性细胞凋亡抑制前列腺癌（PCa）细胞的生长。p53 的激活至少部分解释了 CHO27 在体外的生长抑制作用。此外，腹腔注射 CHO27 抑制了已建立的 PCa 22Rv1 异种移植肿瘤的生长，并伴有 p53 和 p21(Cip1)的诱导。CHO27 可能是开发用于治疗前列腺癌的新型治疗剂的先导化合物。
