Division of Traumatology, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan.
Evid Based Complement Alternat Med. 2012;2012:415231. doi: 10.1155/2012/415231. Epub 2011 Jul 17.
We have investigated the anticancer effects of the dietary isothiocyanate sulforaphane (SFN) on colorectal cancer (CRC), using primary cancer cells lines isolated from five Taiwanese colorectal cancer patients as the model for colorectal cancer. SFN-treated cells accumulated in metaphase (SFN 6.25 μM) and subG1 (SFN 12.5 and 25 μM) as determined by flow cytometry. In addition, treated cells showed nuclear apoptotic morphology that coincided with an activation of caspase-3, and loss of mitochondrial membrane potential (ΔΨm). Incubations at higher SFN doses (12.5 and 25 μM) resulted in cleavage of procaspase-3 and elevated caspase-2, -3, -8, and -9 activity, suggesting that the induction of apoptosis and the sulforaphane-induced mitosis delay at the lower dose are independently regulated. Daily SFN s.c. injections (400 micromol/kg/d for 3 weeks) in severe combined immunodeficient mice with primary human CRC (CP1 to CP5) s.c. tumors resulted in a decrease of mean tumor weight by 70% compared with vehicle-treated controls. Our findings suggest that, in addition to the known effects on cancer prevention, sulforaphane may have antitumor activity in established colorectal cancer.
我们研究了饮食中的异硫氰酸酯萝卜硫素（SFN）对结直肠癌（CRC）的抗癌作用，使用从五位台湾结直肠癌患者中分离的原发性癌细胞系作为结直肠癌模型。SFN 处理的细胞在中期（SFN 6.25μM）和亚 G1（SFN 12.5 和 25μM）积累，如流式细胞术所示。此外，处理后的细胞显示出核凋亡形态，与 caspase-3 的激活以及线粒体膜电位（ΔΨm）的丧失相一致。在更高的 SFN 剂量（12.5 和 25μM）孵育下，导致前 caspase-3 的裂解和 caspase-2、-3、-8 和 -9 活性的升高，这表明凋亡的诱导和较低剂量下的 SFN 诱导的有丝分裂延迟是独立调节的。每日皮下注射 SFN（400 微米ol/kg/d，持续 3 周）在皮下带有原发性人 CRC（CP1 至 CP5）的严重联合免疫缺陷小鼠中，与用载体处理的对照组相比，平均肿瘤重量减少了 70%。我们的研究结果表明，除了对癌症预防的已知作用外，萝卜硫素在已建立的结直肠癌中可能具有抗肿瘤活性。
