Chitotriose Enhanced Antitumor Activity of Doxorubicin through <i>Egr1</i> Upregulation in MDA-MB-231 Cells
Heng Li,
Ke Ji,
Peng Liu,
Yan Geng,
Jinsong Gong,
Chao Zhang,
Zhenzhong Ding,
Zhenghong Xu,
Jinsong Shi
Affiliations
Heng Li
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China
Ke Ji
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China
Peng Liu
Institute of Edible Fungi, Shanghai Academy of Agricultural Sciences, Shanghai 201403, China
Yan Geng
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China
Jinsong Gong
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China
Chao Zhang
Yangzhou Rixing Bio-Tech Co., Ltd., Gaoyou 225601, China
Zhenzhong Ding
Yangzhou Rixing Bio-Tech Co., Ltd., Gaoyou 225601, China
Zhenghong Xu
National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China
Jinsong Shi
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China
Dietary supplementation is proposed as a strategy to reduce the side effects of conventional chemotherapy for triple-negative breast cancer (TNBC). Chitosan oligosaccharides (COS), a functional carbohydrate, have been identified to potentially inhibit cancer cell proliferation. However, a detailed investigation is required to fully understand its exact influence, particularly in terms of COS composition. The antitumor activities of COS oligomers and its monomer of glucosamine, when combined with doxorubicin separately, were evaluated in MDA-MB-231 cells. Chitotriose was identified to have the most significant synergistic effect. Preincubation with chitotriose was observed to promote the entry of doxorubicin into the cell nuclei and induce morphological changes in the cells. Mechanism analysis at the transcriptional level revealed that the early growth response 1 (Egr1) gene was a key regulator in enhancing the suppressive effect. This gene was found to modulate the activity of its downstream gene, growth arrest, and DNA damage-inducible alpha (Gadd45a). The role of Egr1 was confirmed through a small interfering RNA test and function assay. These findings provide insight into the effect and underlying mechanism of chitotriose supplementation for TNBC therapy.
