Metabolic Alterations Induced by Kudingcha Lead to Cancer Cell Apoptosis and Metastasis Inhibition

Abstract

Kudingcha is implicated in alleviating metabolic disorders in traditional Chinese medicine. However, the role of Kudingcha, one of the Ligustrum robustum species, in metabolic regulations and its antitumor activity in triple-negative breast cancer (TNBC) remains to be determined. Two breast cancer cell lines and immunocompetent and immunodeficient mice were used to evaluate the therapeutic effects of Kudingcha treatment. The production of reactive oxygen species (ROS) and glucose uptake were examined by flow cytometry. Metabolic shift was examined by metabonomics and western blot analysis. In this study, we found that aqueous extract of Kudingcha dose dependently inhibited cell growth and induced apoptosis in vitro and in vivo. Moreover, Kudingcha supplementation significantly reduced cancer metastasis. Kudingcha significantly inhibited glycolysis and glutamine metabolism. In addition, we demonstrated that the antitumor effects of Kudingcha were dependent on ROS production, which was increased by β-oxidation and oxidative phosphorylation. These findings provide a novel potential benefit of Kudingcha from targeting the cancer metabolism.

Disclosure Statement

There are no conflicts to declare.

Funding

This research was supported by the State Key Research and Development plan (Grant No. 2017YFD0400200), the National Natural Science Foundation of China (Grant Nos. 31771539 [YQ.C], 31872794 [Dan.Su]), the key Research and Development Program of Jiangsu province (Grant No. BE2018624), the general program of Natural Science Foundation of Jiangsu province (Grant Nos. BK20181346).

Authors’ Contributions

Shenglong Zhu and Yong Q. Chen conceived and designed the experiments; Shenglong Zhu, Yuelin Tong, Jingwei Zhang, Xuan Jiang, Qingwen He, Dou dou Zhu, Xuyang Lu, Lengyun Wei, and Guangxiao Lin performed the experiments; Shenglong Zhu, Guangxiao Lin analyzed the results; and Shenglong Zhu wrote the manuscript.