Jiang Jiahua, Slivova Veronika, Sliva Daniel
Cancer Research Laboratory, Methodist Research Institute, Indianapolis, IN 46202, USA.
Int J Oncol. 2006 Sep;29(3):695-703.
Ganoderma lucidum, an oriental medical mushroom, has been used in Asia for the prevention and treatment of a variety of diseases, including cancer. We have previously demonstrated that G. lucidum inhibits growth and induces cell cycle arrest at G0/G1 phase through the inhibition of Akt/NF-kappaB signaling in estrogen-independent human breast cancer cells. However, the molecular mechanism(s) responsible for the inhibitory effects of G. lucidum on the proliferation of estrogen-dependent (MCF-7) and estrogen-independent (MDA-MB-231) breast cancer cells remain to be elucidated. Here, we show that G. lucidum inhibited the proliferation of breast cancer MCF-7 and MDA-MB-231 cells by the modulation of the estrogen receptor (ER) and NF-kappaB signaling. Thus, G. lucidum down-regulated the expression of ERalpha in MCF-7 cells but did not effect the expression of ERbeta in MCF-7 and MDA-MB-231 cells. In addition, G. lucidum inhibited estrogen-dependent as well as constitutive transactivation activity of ER through estrogen response element (ERE) in a reporter gene assay. G. lucidum decreased TNF-alpha-induced (MCF-7) as well as constitutive (MDA-MB-231) activity of NF-kappaB. The inhibition of ER and NF-kappaB pathways resulted in the down-regulation of expression of c-myc, finally suppressing proliferation of estrogen-dependent as well as estrogen-independent cancer cells. Collectively, these results suggest that G. lucidum inhibits proliferation of human breast cancer cells and contain biologically active compounds with specificity against estrogen receptor and NF-kappaB signaling, and implicate G. lucidum as a suitable herb for chemoprevention and chemotherapy of breast cancer.
灵芝是一种东方药用真菌，在亚洲已被用于预防和治疗包括癌症在内的多种疾病。我们之前已经证明，灵芝通过抑制雌激素非依赖性人乳腺癌细胞中的Akt/NF-κB信号传导来抑制生长并诱导细胞周期停滞在G0/G1期。然而，灵芝对雌激素依赖性（MCF-7）和雌激素非依赖性（MDA-MB-231）乳腺癌细胞增殖的抑制作用的分子机制仍有待阐明。在这里，我们表明灵芝通过调节雌激素受体（ER）和NF-κB信号传导来抑制乳腺癌MCF-7和MDA-MB-231细胞的增殖。因此，灵芝下调了MCF-7细胞中ERα的表达，但对MCF-7和MDA-MB-231细胞中ERβ的表达没有影响。此外，在报告基因测定中，灵芝通过雌激素反应元件（ERE）抑制雌激素依赖性以及ER的组成型反式激活活性。灵芝降低了TNF-α诱导的（MCF-7）以及NF-κB的组成型（MDA-MB-231）活性。对ER和NF-κB途径的抑制导致c-myc表达下调，最终抑制雌激素依赖性和雌激素非依赖性癌细胞的增殖。总的来说，这些结果表明灵芝抑制人乳腺癌细胞的增殖，并含有对雌激素受体和NF-κB信号传导具有特异性的生物活性化合物，这表明灵芝是一种适合用于乳腺癌化学预防和化疗的草药。
