Chen X G, Li Y, Yan C H, Li L N, Han R
Department of Pharmacology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing.
J Asian Nat Prod Res. 2001;3(1):63-75. doi: 10.1080/10286020108042840.
Salvia miltiorrhiza is a traditional Chinese medicine which has been well documented for its anti-cancer effects. Based on the structure of danshinone, one of the active compounds derived from Salvia miltiorrhiza, we synthesized a simplified phenolic analog, S-3-1, and tried to explore its possible actions in preventing the development of cancer. With the Ames test, S-3-1 was found to efficiently suppress the mutagenicity of benzo[alpha]pyrene. This result is consistent with the inhibitory effect of S-3-1 on the activation of benzo[alpha]pyrene by hepatic microsomal enzymes. Besides the anti-initiation effects, S-3-1 could significantly inhibit the croton oil-induced increase of mouse skin epithermal ornithine decarboxylase activity. Moreover, S-3-1 quenched both superoxide and hydroxyl free radicals whereas it inhibited lipid peroxidation in the in vitro model. These results suggest that S-3-1 might act as anti-initiation and anti-promotion agents through reversing the biochemical alterations induced by carcinogen during carcinogenesis. Therefore, we further investigated the effects of S-3-1 on carcinogenesis. In vitro, S-3-1 inhibited the benzo[alpha]pyrene-induced transformation of V79 Chinese hamster lung fibroblasts. At 10-40 mg/kg, S-3-1 was found to inhibit the development of DMBA/croton oil-induced skin papilloma in mice through decreasing the incidence of papilloma, prolonging the latent period of tumor occurrence and reducing tumor number per mouse in a dose-dependent manner. We concluded from this study that S-3-1 might be developed as a new chemopreventive drug.
丹参是一种传统中药，其抗癌作用已有充分记载。基于丹参中的一种活性化合物丹参酮的结构，我们合成了一种简化的酚类类似物S-3-1，并试图探索其在预防癌症发生中的可能作用。通过艾姆斯试验发现，S-3-1能有效抑制苯并[a]芘的致突变性。这一结果与S-3-1对肝微粒体酶激活苯并[a]芘的抑制作用一致。除了抗启动作用外，S-3-1还能显著抑制巴豆油诱导的小鼠皮肤表皮鸟氨酸脱羧酶活性的增加。此外，在体外模型中，S-3-1能清除超氧自由基和羟自由基，同时抑制脂质过氧化。这些结果表明，S-3-1可能通过逆转致癌物在致癌过程中诱导的生化改变而发挥抗启动和抗促进剂的作用。因此，我们进一步研究了S-3-1对致癌作用的影响。在体外，S-3-1抑制苯并[a]芘诱导的V79中国仓鼠肺成纤维细胞的转化。在10-40mg/kg剂量下，发现S-3-1能通过降低乳头状瘤的发生率、延长肿瘤发生的潜伏期并以剂量依赖的方式减少每只小鼠的肿瘤数量，从而抑制二甲基苯并蒽/巴豆油诱导的小鼠皮肤乳头状瘤的发生。我们从这项研究中得出结论，S-3-1可能被开发成为一种新的化学预防药物。
