Chang Jong Sun, Bae Joon Tae, Oh Eun Jung, Kim Ji Young, Park Sun Hee, Lee Kap Rang
Bioindustry Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, Republic of Korea.
J Med Food. 2009 Jun;12(3):493-500. doi: 10.1089/jmf.2008.1050.
Hypsizigus marmoreus has recently become a popular edible mushroom in Asia. Despite its extensive use, the underlying mechanisms of the anticarcinogenic effects on the initiation stage are not precisely known. Therefore, methanol extracts from H. marmoreus were prepared and then tested for antiproliferative effects in cancer cells and antimutagenic activities as well as mutagenic capacity using the Ames Salmonella mutagenicity test. In addition, the effects on the phase I drug metabolizing enzymes, phase II detoxifying enzymes, and antioxidative activities were evaluated in livers from mice pretreated with methanol extracts from H. marmoreus and challenged with benzo[a]pyrene (B[a]P). In the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, methanol extracts from H. marmoreus displayed a dose-dependent inhibitory effect against human hepatocarcinoma and colon carcinoma cells. However, equivalent doses did not induce mutagenicity when tested with Salmonella typhimurium TA98 and TA100 while exhibiting antimutagenicity against direct-acting and indirect-acting mutagens. Methanol extracts from H. marmoreus strongly decreased total cytochrome P450 and activity of ethoxyresorufin deethylase after B[a]P challenge. Further investigation revealed that methanol extracts from H. marmoreus decreased protein levels of cytochrome P450 IAI isozyme induced by B[a]P. Methanol extracts from H. marmoreus increased the content of glutathione and activity of glutathione S-transferase. This also induced the activity of quinone reductase, an enzyme well known to be anticarcinogenic. The results of the present study therefore demonstrated that methanol extracts from H. marmoreus may have antimutagenic effects, inhibiting the mutagenicity of some mutagens, particularly indirect-acting B[a]P. The mechanism of this antimutagenicity may be the induction of the activity of phase II enzymes, as well as the ability to reduce phase I metabolic-activating enzymes in mouse liver.
真姬菇最近已成为亚洲一种受欢迎的食用蘑菇。尽管其应用广泛，但对其在致癌起始阶段抗癌作用的潜在机制尚不完全清楚。因此，制备了真姬菇的甲醇提取物，然后使用艾姆斯沙门氏菌致突变试验检测其对癌细胞的抗增殖作用、抗诱变活性以及诱变能力。此外，在用真姬菇甲醇提取物预处理并接触苯并[a]芘（B[a]P）的小鼠肝脏中，评估了其对Ⅰ相药物代谢酶、Ⅱ相解毒酶和抗氧化活性的影响。在3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐试验中，真姬菇甲醇提取物对人肝癌细胞和结肠癌细胞显示出剂量依赖性抑制作用。然而，当用鼠伤寒沙门氏菌TA98和TA100检测时，同等剂量并未诱导诱变，同时对直接作用和间接作用的诱变剂表现出抗诱变作用。真姬菇甲醇提取物在B[a]P刺激后显著降低了总细胞色素P450和乙氧基异吩恶唑酮脱乙基酶的活性。进一步研究表明，真姬菇甲醇提取物降低了B[a]P诱导的细胞色素P450 IAI同工酶的蛋白水平。真姬菇甲醇提取物增加了谷胱甘肽含量和谷胱甘肽S-转移酶的活性。这还诱导了醌还原酶的活性，醌还原酶是一种众所周知的抗癌酶。因此，本研究结果表明，真姬菇甲醇提取物可能具有抗诱变作用，抑制某些诱变剂的诱变作用，特别是间接作用的B[a]P。这种抗诱变作用的机制可能是诱导Ⅱ相酶的活性，以及降低小鼠肝脏中Ⅰ相代谢激活酶的能力。
