Singh S V, Pan S S, Srivastava S K, Xia H, Hu X, Zaren H A, Orchard J L
Cancer Research Laboratory, Mercy Hospital of Pittsburgh, Pennsylvania 15219, USA.
Biochem Biophys Res Commun. 1998 Mar 27;244(3):917-20. doi: 10.1006/bbrc.1998.8352.
This study was undertaken to elucidate the mechanism of organ specificity and differential efficacy of garlic organosulfides (OSCs) [diallyl sulfide (DAS), diallyl disulfide (DADS), diallyl trisulfide (DATS), dipropyl sulfide (DPS) and dipropyl disulfide (DPDS)] in preventing benzo(a)pyrene (BP)-induced tumorigenesis in mice. The results of the present study reveal a good correlation between chemopreventive efficacies of garlic OSCs and their inductive effects on the expression of NAD(P)H:quinone oxidoreductase (NQO), an enzyme implicated in the detoxification of activated quinone metabolites of BP. Treatment of mice with DADS and DATS, which are potent inhibitors of BP-induced forestomach tumorigenesis, resulted in a statistically significant increase (2.4- and 1.5-fold, respectively) in forestomach NQO activity. In addition, DADS and DATS were much more potent inducers of forestomach NQO activity than DAS, which is a weak inhibitor of BP-induced forestomach tumorigenesis than the former compounds. Propyl-group containing OSCs (DPS and DPDS), which do not inhibit BP-induced tumorigenesis, did not affect forestomach NQO activity. Similar to forestomach, a good correlation was also observed between effects of these OSCs against BP-induced pulmonary tumorigenesis and their effects on NQO expression in the lung. For example, treatment of mice with DAS, which is a potent inhibitor of BP-induced pulmonary tumorigenesis, resulted in about 3.2-fold increase in pulmonary NQO activity. On the other hand, this activity was increased by about 1.5-fold upon DATS administration, which does not inhibit BP-induced cancer of the lung. In conclusion, our results suggest that induction of NQO may be important in anti-cancer effects of garlic OSCs.
本研究旨在阐明大蒜有机硫化物（OSCs）[二烯丙基硫醚（DAS）、二烯丙基二硫醚（DADS）、二烯丙基三硫醚（DATS）、二丙基硫醚（DPS）和二丙基二硫醚（DPDS）]在预防苯并(a)芘（BP）诱导的小鼠肿瘤发生过程中的器官特异性机制和不同疗效。本研究结果显示，大蒜OSCs的化学预防效果与其对NAD(P)H:醌氧化还原酶（NQO）表达的诱导作用之间存在良好的相关性，NQO是一种与BP活性醌代谢物解毒有关的酶。用DADS和DATS处理小鼠，它们是BP诱导的前胃肿瘤发生的有效抑制剂，导致前胃NQO活性有统计学意义的显著增加（分别为2.4倍和1.5倍）。此外，DADS和DATS诱导前胃NQO活性的能力比DAS强得多，DAS对BP诱导的前胃肿瘤发生的抑制作用比前两者弱。含丙基的OSCs（DPS和DPDS）不抑制BP诱导的肿瘤发生，也不影响前胃NQO活性。与前胃相似，这些OSCs对BP诱导的肺肿瘤发生的作用与其对肺中NQO表达的影响之间也观察到良好的相关性。例如，用DAS处理小鼠，DAS是BP诱导的肺肿瘤发生的有效抑制剂，导致肺NQO活性增加约3.2倍。另一方面，给予DATS后该活性增加约1.5倍，DATS不抑制BP诱导的肺癌。总之，我们的结果表明，诱导NQO可能在大蒜OSCs的抗癌作用中起重要作用。
