Spatial Metabolomics Profiling Reveals Curcumin Induces Metabolic Reprogramming in Three-Dimensional Tumor Spheroids

Author:

Zhu Zihan123,Zhang Yaqi12,Wang Lei12,Geng Haoyuan12,Li Min12,Chen Shiping12,Wang Xiao12ORCID,Chen Panpan12,Sun Chenglong12ORCID,Zhang Chao4

Affiliation:

1. Key Laboratory for Natural Active Pharmaceutical Constituents Research in Universities of Shandong Province, School of Pharmaceutical Sciences, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, China

2. Key Laboratory for Applied Technology of Sophisticated Analytical Instruments of Shandong Province, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, China

3. School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China

4. Department of Pediatrics, Qilu Hospital of Shandong University, Jinan 250012, China

Abstract

Curcumin is widely recognized for its diverse antitumor properties, ranging from breast cancer to many other types of cancers. However, its role in the tumor microenvironment remains to be elucidated. In this study, we established a 3D tumor spheroids model that can simulate the growth environment of tumor cells and visualized the antitumor metabolic alteration caused by curcumin using mass spectrometry imaging technology. Our results showed that curcumin not only exerts a profound impact on the growth and proliferation of breast cancer cells but in situ multivariate statistical analysis also reveals the significant effect on the overall metabolic profile of tumor spheroids. Meanwhile, our visualization map characterized curcumin metabolic processes of reduction and glucuronidation in tumor spheroids. More importantly, abnormal metabolic pathways related to lipid metabolism and polyamine metabolism were also remodeled at the metabolite and gene levels after curcumin intervention. These insights deepen our comprehension of the regulatory mechanism of curcumin on the tumor metabolic network, furnishing powerful references for antitumor treatment.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Shandong Province

Shandong Province Science and Technology Small and Medium Enterprises Innovation Ability Enhancement Project

Taishan Scholars Program of Shandong Province

Publisher

MDPI AG

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