2. Academic Validation
  3. Antiproliferation Activity and Mechanism of c9, t11, c15-CLNA and t9, t11, c15-CLNA from Lactobacillus plantarum ZS2058 on Colon Cancer Cells

Antiproliferation Activity and Mechanism of c9, t11, c15-CLNA and t9, t11, c15-CLNA from Lactobacillus plantarum ZS2058 on Colon Cancer Cells

  • Molecules. 2020 Mar 9;25(5):1225. doi: 10.3390/molecules25051225.
Qing Ren 1 2,  Bo Yang 1 2,  Guangzhen Zhu 2,  Shunyu Wang 3,  Chengli Fu 3,  Hao Zhang 1 2 4 5,  R Paul Ross 6 7,  Catherine Stanton 6 7 8,  Haiqin Chen 1 2,  Wei Chen 1 2 4 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
  • 2 School of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
  • 3 Zhejiang Liziyuan Food Co., Ltd., Jinhua 321015, China.
  • 4 National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China.
  • 5 Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch, Wuxi 214122, China.
  • 6 International Joint Research Center for Probiotics & Gut Health, Jiangnan University, Wuxi 214122, China.
  • 7 APC Microbiome Ireland, University College Cork, T12 K8AF Cork, Ireland.
  • 8 Teagasc Food Research Centre, Moorepark, Fermoy, P61 C996 Co. Cork, Ireland.
  • 9 Beijing Innovation Centre of Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing 100048, China.
PMID: 32182796 DOI: 10.3390/molecules25051225
Abstract

Conjugated linolenic acid (CLNA) is a type of ω-3 fatty acid which has been proven to have a series of benefits. However, there is no study about the function of Lactobacillus-derived CLNA isomer. Lactobacillus plantarum ZS2058 has been proven to manifest comprehensive functions and can produce CLNA. To investigate the specific functions of CLNA produced by this probiotic bacterium, two different conjugated α-linolenic acid (CLNA) isomers were successfully isolated. These isoforms, CLNA1 (c9, t11, c15-CLNA, purity 97.48%) and CLNA2 (c9, t11, t15-CLNA, purity 99.00%), both showed the ability to inhibit the growth of three types of colon Cancer cells in a time- and concentration-dependent manner. In addition, the expression of MDA in Caco-2 cells was increased by CLNA1 or CLNA2, which indicated that lipid peroxidation was related to the antiproliferation activity of CLNAs. An examination of the key protein of Pyroptosis showed that CLNA1 induced the cleavage of Caspase-1 and gasdermin-D, while CLNA2 induced the cleavage of caspase-4, 5 and gasdermin-D. The addition of relative inhibitors could alleviate the Pyroptosis by CLNAs. CLNA1 and CLNA2 showed no effect on Caspase-3, 7, 9 and PARP-1, which were key proteins associated with Apoptosis. No sub-diploid apoptotic peak appeared in the result of PI single staining test. In conclusion, CLNA1 activated Caspase-1 and induced Caco-2 cell Pyroptosis, whereas CLNA2 induced Pyroptosis through the caspase-4/5-mediated pathway. The inhibition of Caco-2 cells by the two isomers was not related to Apoptosis. This is the first study on the function of Lactobacillus-derived CLNA isomer. The inhibition pathway of Lactobacillus-derived CLNA isomer on colon Cancer cells were proved.

Keywords

apoptosis; caco-2 cell; conjugated linolenic acid; lipid peroxidation; pyroptosis.

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