J Cancer 2018; 9(18):3382-3393. doi:10.7150/jca.25136

Research Paper

Compound Fuling Granule Suppresses Ovarian Cancer Development and Progression by disrupting mitochondrial function, galactose and fatty acid metabolism

Shanming Ruan1,#, Zhiqian Zhang2,3,#, Xinxin Tian2,4,#, Dawei Huang5,#, Wenhong Liu6, Bo Yang7, Minhe Shen1, Fangfang Tao6,✉

1. Department of Medical Oncology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310003, Zhejiang, China
2. Tianjin International Joint Academy of Biomedicine (TJAB), Tianjin 300457, People's Republic of China.
3. State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, People's Republic of China.
4. Department of Biochemistry and Biophysics, Texas A&M University and Texas AgriLife Research, College Station, TX 77843-2128, USA.
5. Department of Chinese Medicine, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310003, Zhejiang, China
6. Department of Immunology and Microbiology, Basic Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
7. School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
# These authors contributed equally to this work and should be considered as co-first authors.

Abstract

Our previous studies have demonstrated that the compound fuling granule (CFG), a traditional Chinese medicine, suppresses ovarian cancer cell growth, migration and metastasis. However, the underlying mechanisms remain to be fully elucidated. In this study, we found that CFG could induce mitochondrial fragmentation, mitochondrial membrane potential reduction and cytochrome c release in ovarian SKOV3 cancer cells. In addition, both metabolomics and transcriptomics approaches were applied to illustrate the systemic mechanism of CFG on ovarian cancer formation and progression. To this end, we established two tumor-bearing mice models with subcutaneous injection or tail intravenous injection. Functionally, administration of CFG suppresses in situ tumor growth and distant lung metastasis. Subsequently, gas chromatography-mass spectrometry (GC-MS) was applied to determine the metabolic alterations among the plasma samples from these in vivo models. In the subcutaneous injection model, 26 distinguishable metabolites were identified and 12 metabolic pathways were reprogrammed. Meanwhile, 19 metabolites involved in 7 metabolic pathways showed significant differences in the tail intravenous injection model. Importantly, integrative metabolomics and transcriptomics analysis showed these metabolites were highly associated with galactose metabolism and fatty acid metabolism. This study suggests that CFG may suppress ovarian cancer cell proliferation and metastasis by regulating mitochondrion-related energy metabolisms.

Keywords: Compound fuling granule, Mitochondrion, Ovarian cancer, Galactose metabolism, Fatty acid metabolism

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How to cite this article:
Ruan S, Zhang Z, Tian X, Huang D, Liu W, Yang B, Shen M, Tao F. Compound Fuling Granule Suppresses Ovarian Cancer Development and Progression by disrupting mitochondrial function, galactose and fatty acid metabolism. J Cancer 2018; 9(18):3382-3393. doi:10.7150/jca.25136. Available from http://www.jcancer.org/v09p3382.htm