Kim Mi-Sung, Kwon Jung Yeon, Kang Nam Joo, Lee Ki Won, Lee Hyong Joo
Department of Food Science and Biotechnology, Seoul National University, Seoul, Korea.
Ann N Y Acad Sci. 2009 Aug;1171:479-83. doi: 10.1111/j.1749-6632.2009.04692.x.
Mutations in Ras play a critical role in the development of human cancers, including breast cancer. We investigated the possible antiproliferative effects of the naturally occurring dihydrochalcone phloretin [2',4',6'-trihydroxy-3-(4-hydroxyphenyl)-propiophenone] on H-Ras-transformed MCF10A human breast epithelial (H-Ras MCF10A) cells. Phloretin suppressed H-Ras MCF10A cell proliferation in a dose-dependent manner and induced nuclear condensation in the cells, indicating that phloretin-induced cell death occurs mainly via the induction of apoptosis. Prominent upregulation of p53 and Bax and cleavage of poly (ADP)-ribose polymerase were also detected in the phloretin-treated cells. Finally, phloretin markedly increased caspase-3 activity as well as JNK and p38 mitogen-activated protein kinase signaling. Our findings suggest that the phloretin-induced apoptosis of breast tumor cells contributes to the chemopreventive potential of phloretin against breast cancer.
Ras基因的突变在包括乳腺癌在内的人类癌症发展过程中起着关键作用。我们研究了天然存在的二氢查耳酮根皮素[2',4',6'-三羟基-3-(4-羟基苯基)-苯丙酮]对H-Ras转化的MCF10A人乳腺上皮（H-Ras MCF10A）细胞可能的抗增殖作用。根皮素以剂量依赖性方式抑制H-Ras MCF10A细胞增殖，并诱导细胞中的核浓缩，表明根皮素诱导的细胞死亡主要通过诱导凋亡发生。在根皮素处理的细胞中还检测到p53和Bax的显著上调以及聚（ADP）-核糖聚合酶的裂解。最后，根皮素显著增加了caspase-3活性以及JNK和p38丝裂原活化蛋白激酶信号传导。我们的研究结果表明，根皮素诱导的乳腺肿瘤细胞凋亡有助于根皮素对乳腺癌的化学预防潜力。
