Fu Sophia L, Wallner Sabine R, Bowne Wilbur B, Hagler Michael D, Zenilman Michael E, Gross Richard, Bluth Martin H
Department of Surgery, SUNY Downstate Medical Center, Brooklyn, New York 11203, USA.
J Surg Res. 2008 Jul;148(1):77-82. doi: 10.1016/j.jss.2008.03.005. Epub 2008 Apr 11.
We have previously demonstrated that sophorolipids, a class of easily chemoenzymatically modifiable glycolipids, possess anti-inflammatory effects in vitro and in vivo. Since glycolipids have been shown to have anticancer activity, we investigated the effects of sophorolipids and their derivatives against pancreatic cancer.
Human pancreatic carcinoma cells were treated with increasing concentrations of sophorolipid natural mixture or select derivatives (ethyl ester, methyl ester, ethyl ester monoacetate, ethyl ester diacetate, acidic sophorolipid [AS], lactonic sophorolipid diacetate [LSD]) for 24 h and assessed for cell necrosis (cytotoxicity-lactate dehydrogenase release). Controls consisted of cells treated with media or vehicle alone and sophorolipid treatment of peripheral blood mononuclear cells.
Sophorolipids demonstrated anticancer activity against human pancreatic carcinoma cells. Natural mixture mediated consistent cytotoxicity at all doses tested (20 +/- 4%). However, methyl ester derivative mediated much greater levels of cytotoxicity (63 +/- 5%) compared with other derivatives (ethyl ester diacetate, 36 +/- 6%, ethyl ester monoacetate, 18 +/- 7%; P < 0.05). In contrast, LSD- and AS-mediated toxicity was inversely proportional with dose (LSD, 40.3% at 0.5 mg/mL, 3.4% at 2.0 mg/mL; AS, 49% at 0.5 mg/mL, 0% at 2.0 mg/mL). Sophorolipid treatment did not affect peripheral blood mononuclear cells at all doses tested.
These results suggest that sophorolipids and select derivatives may be effective in treating human pancreatic cancer. Furthermore select derivatives may use different mechanisms toward this end. The ability to chemoenzymatically modify sophorolipids can provide effective lead compounds toward the treatment of pancreatic cancer.
我们之前已经证明，槐糖脂是一类易于通过化学酶法修饰的糖脂，在体外和体内均具有抗炎作用。由于糖脂已被证明具有抗癌活性，我们研究了槐糖脂及其衍生物对胰腺癌的影响。
用浓度递增的槐糖脂天然混合物或特定衍生物（乙酯、甲酯、乙酯单乙酸酯、乙酯二乙酸酯、酸性槐糖脂[AS]、内酯型槐糖脂二乙酸酯[LSD]）处理人胰腺癌细胞24小时，并评估细胞坏死情况（细胞毒性-乳酸脱氢酶释放）。对照组包括仅用培养基或溶剂处理的细胞以及用槐糖脂处理的外周血单核细胞。
槐糖脂对人胰腺癌细胞具有抗癌活性。天然混合物在所有测试剂量下均介导一致的细胞毒性（20±4%）。然而，甲酯衍生物介导的细胞毒性水平比其他衍生物（乙酯二乙酸酯，36±6%；乙酯单乙酸酯，18±7%；P<0.05）高得多（63±5%）。相比之下，LSD和AS介导的毒性与剂量成反比（LSD，0.5mg/mL时为40.3%，2.0mg/mL时为3.4%；AS，0.5mg/mL时为49%，2.0mg/mL时为0%）。在所有测试剂量下，槐糖脂处理对外周血单核细胞均无影响。
这些结果表明，槐糖脂及其特定衍生物可能对治疗人类胰腺癌有效。此外，特定衍生物可能为此采用不同的机制。通过化学酶法修饰槐糖脂的能力可为胰腺癌治疗提供有效的先导化合物。
