Nakagawa H, Tsuta K, Kiuchi K, Senzaki H, Tanaka K, Hioki K, Tsubura A
Department of Pathology II and Department of Surgery II, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan.
Carcinogenesis. 2001 Jun;22(6):891-7. doi: 10.1093/carcin/22.6.891.
Diallyl disulfide (DADS) is an oil-soluble organosulfur compound found in garlic. The effect of synthetic DADS on the growth of estrogen receptor (ER)-positive (KPL-1 and MCF-7) and -negative (MDA-MB-231 and MKL-F) human breast cancer cell lines was examined. In an in vitro MTT assay, regardless of ER status, DADS at an IC(50) of 1.8-18.1 microM after 72 h incubation caused inhibition of growth in all four cell lines examined. Growth inhibition was due to apoptosis as seen by the appearance of a sub G1 fraction. In MDA-MB-231 cells, the apoptosis cascade comprised up-regulation of Bax protein (142%), down-regulation of Bcl-X(L) protein (38%) and activation of caspase-3 (438%) compared with controls. In an in vivo assay by orthotopic (right thoracic mammary fat pad) transplantation of KPL-1 cells in female nude mice, intraperitoneal injection of 1 or 2 mg DADS three times a week from the day of tumor cell inoculation until the end of the experiment (after 35 days) caused growth retardation and 43% reductions in primary tumor weight, respectively, compared with DADS-untreated mice without apparent side effects. Cell proliferation as evaluated by proliferating cell nuclear antigen (PCNA)-labeling in transplanted tumor of DADS-untreated mice was 59.6%, and 1 and 2 mg DADS-treated mice was 44.6 and 44.5%, respectively. In MDA-MB-231 cells, DADS antagonized the effect of linoleic acid (LA), a potent breast cancer cell stimulator (at DADS = 1.8 microM and LA > or = 6.5x10(2) microM concentration), and synergized the effect of eicosapentaenoic acid (EPA), a potent breast cancer cell suppressor (at DADS >3 x 10(-3) microM and EPA > 6.3 x 10(-1) microM concentration). Thus, DADS could be a promising anticancer agent for both hormone-dependent and -independent breast cancers, and may harmonize with polyunsaturated fatty acids known as modulators of breast cancer cell growth.
二烯丙基二硫化物（DADS）是一种存在于大蒜中的油溶性有机硫化合物。研究了合成的DADS对雌激素受体（ER）阳性（KPL-1和MCF-7）及阴性（MDA-MB-231和MKL-F）人乳腺癌细胞系生长的影响。在体外MTT试验中，无论ER状态如何，孵育72小时后，IC（50）为1.8 - 18.1微摩尔的DADS对所有四种检测的细胞系的生长均有抑制作用。生长抑制是由于出现亚G1期细胞群而导致的细胞凋亡。在MDA-MB-231细胞中，与对照组相比，凋亡级联反应包括Bax蛋白上调（142%）、Bcl-X（L）蛋白下调（38%）以及caspase-3激活（438%）。在雌性裸鼠中通过原位（右胸乳腺脂肪垫）移植KPL-1细胞进行的体内试验中，从接种肿瘤细胞之日起至实验结束（35天后），每周三次腹腔注射1或2毫克DADS，与未用DADS处理的小鼠相比，分别导致生长迟缓以及原发性肿瘤重量减少43%，且无明显副作用。通过增殖细胞核抗原（PCNA）标记评估，未用DADS处理的小鼠移植瘤中的细胞增殖率为59.6%，而1毫克和2毫克DADS处理的小鼠分别为44.6%和44.5%。在MDA-MB-231细胞中，DADS拮抗了亚油酸（LA，一种强效乳腺癌细胞刺激剂，在DADS = 1.8微摩尔且LA≥6.5×10（2）微摩尔浓度时）的作用，并协同了二十碳五烯酸（EPA，一种强效乳腺癌细胞抑制剂，在DADS＞3×10（-3）微摩尔且EPA＞6.3×10（-1）微摩尔浓度时）的作用。因此，DADS可能是一种对激素依赖性和非激素依赖性乳腺癌均有前景的抗癌药物，并且可能与作为乳腺癌细胞生长调节剂的多不饱和脂肪酸协同作用。
