title: In Vitro and in Vivo Anticancer Activity of Sophorolipids to Human Cervical Cancer.
abstract: Six characteristic di-acetylated lactonic sophorolipids with C16:1, C16:0, C18:0, C18:1, C18:2, and C18:3 fatty acid were obtained from Starmerella bombicola CGMCC 1576. In order to confirm their anticancer activity against human cervical cancer cells and reveal the structure-activity relationships, their anti-proliferation effects on HeLa and CaSki cells were estimated. The cytotoxicity of sophorolipid molecules with different degrees of unsaturation was proved to be influenced by carbon chain length of sophorolipids. The longer the carbon chain length, the stronger the cytotoxicity of sophorolipids. The inhibitory mechanism of a di-acetylated lactonic C18:1 sophorolipid on HeLa cells was investigated. The cells developed many features of apoptosis and cell cycle was blocked at G0phase and partly at G2phase. The expression of CHOP and Bip/GRP78 was induced. Caspase-12 and caspase-3 were both activated. However, mitochondrial membrane potential and concentration of cytosolic cytochrome C did not change. The induced apoptosis of HeLa cells was probably triggered through endoplasmic reticulum signaling pathway without involvement of mitochondria. In vivo, 5, 50, and 500 mg/kg lactonic sophorolipids showed 29.90, 41.24, and 52.06 % of inhibition without significant toxicity to tumor-bearing mice, respectively. Our findings may suggest a potential use of sophorolipids in human cervical cancer treatment.
authors: State Key Laboratory of Microbial Technology, Shandong University, Shan Da Nan Road 27, Jinan, Shandong, 250100, China.
authors: Hui
authors: H
authors: Li
authors: State Key Laboratory of Microbial Technology, Shandong University, Shan Da Nan Road 27, Jinan, Shandong, 250100, China.
authors: Wei
authors: W
authors: Guo
authors: State Key Laboratory of Microbial Technology, Shandong University, Shan Da Nan Road 27, Jinan, Shandong, 250100, China.
authors: Xiao-Jing
authors: XJ
authors: Ma
authors: State Key Laboratory of Microbial Technology, Shandong University, Shan Da Nan Road 27, Jinan, Shandong, 250100, China.
authors: Jia-Shan
authors: JS
authors: Li
authors: State Key Laboratory of Microbial Technology, Shandong University, Shan Da Nan Road 27, Jinan, Shandong, 250100, China. songx@sdu.edu.cn.|National Glycoengineering Research Centre, Shandong University, Shan Da Nan Road 27, Jinan, Shandong, 250100, China. songx@sdu.edu.cn.
authors: Xin
authors: X
authors: Song
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006017:Glycolipids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D004718:Saccharomycetales / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D002583:Uterine Cervical Neoplasms / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; D006017:Glycolipids; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse
keywords: Anticancer activity; Human cervical cancer; In vitro; In vivo; Sophorolipids