Sophorolipids and Their Derivatives Are Lethal Against Human Pancreatic Cancer Cells

• Published in: The Journal of surgical research Vol. 148; no. 1; pp. 77 - 82
• Main Authors: Fu, Sophia L., M.D, Wallner, Sabine R., Ph.D, Bowne, Wilbur B., M.D, Hagler, Michael D, Zenilman, Michael E., M.D, Gross, Richard, Ph.D, Bluth, Martin H., M.D., Ph.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.2008; Elsevier
• Subjects: adenocarcinoma; Adenocarcinoma - drug therapy; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell Line, Tumor; cytotoxicity; Dose-Response Relationship, Drug; Gastroenterology. Liver. Pancreas. Abdomen; General aspects; glycolipid; Glycolipids - pharmacology; Humans; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; necrosis; pancreatic cancer; Pancreatic Neoplasms - drug therapy; sophorolipid; Surgery; Tumors; glycolipid; adenocarcinoma; pancreatic cancer; necrosis; sophorolipid; cytotoxicity; Adenocarcinoma; Human; Mortality; Cytotoxicity; Malignant tumor; Glycolipid; Necrosis; Medicine; Treatment; Surgery; Pancreas cancer; Digestive diseases; Derived product; Tumor cell; Cancer; Pancreatic disease
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2008.03.005

Introduction 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. Materials and methods 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. Results 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. Conclusions 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.