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In Vitro and in Vivo Anticancer Activity of Sophorolipids to Human Cervical Cancer

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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 G0 phase and partly at G2 phase. 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.

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Abbreviations

SLs:

Sophorolipids

C18:3 DLSL:

Di-acetylated lactonic SL with a C18:3 fatty acid

C18:2 DLSL:

Di-acetylated lactonic SL with a C18:2 fatty acid

C18:1 DLSL:

Di-acetylated lactonic SL with a C18:1 fatty acid

C18:0 DLSL:

Di-acetylated lactonic SL with a C18:0 fatty acid

C16:1 DLSL:

Di-acetylated lactonic SL with a C16:1 fatty acid

C16:0 DLSL:

Di-acetylated lactonic SL with a C16:0 fatty acid

HPLC:

High-performance liquid chromatography

MTT:

3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenytetrazolium

TEM:

Transmission electron microscopy

MMP:

Mitochondrial membrane potential

ER:

Endoplasmic reticulum

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Acknowledgments

This study was funded by the National Natural Science Foundation of China (No. 30970052 and No. 31270089), Natural Science Foundation of Shandong Province (ZR2009BZ002), and National Key Technology R&D Program (2011BAC02B04). We thank Professor Yaoqin Gong for providing HeLa cells. We also thank Professor Junying Miao for donating HUVECs cells.

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Authors and Affiliations

  1. State Key Laboratory of Microbial Technology, Shandong University, Shan Da Nan Road 27, Jinan, Shandong, 250100, China

    Hui Li, Wei Guo, Xiao-jing Ma, Jia-shan Li & Xin Song

  2. National Glycoengineering Research Centre, Shandong University, Shan Da Nan Road 27, Jinan, Shandong, 250100, China

    Xin Song

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  1. Hui Li
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  2. Wei Guo
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Correspondence to Xin Song.

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Li, H., Guo, W., Ma, Xj. et al. In Vitro and in Vivo Anticancer Activity of Sophorolipids to Human Cervical Cancer. Appl Biochem Biotechnol 181, 1372–1387 (2017). https://doi.org/10.1007/s12010-016-2290-6

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