Schisantherin A Inhibits Cell Proliferation by Regulating Glucose Metabolism Pathway in Hepatocellular Carcinoma

Overview

Journal Front Pharmacol

Date 2022 Nov 25

PMID 36425581

Authors

Fan Feng

Lianhong Pan

Jiaqin Wu

Mingying Liu

Long He

Li Yang

Wei Zhou

Affiliations

Soon will be listed here.

Abstract

Schisantherin A (STA) is a traditional Chinese medicine extracted from the plant , which has a wide range of anti-inflammatory, antioxidant, and other pharmacological effects. This study investigates the anti-hepatocellular carcinoma effects of STA and the underlying mechanisms. STA significantly inhibits the proliferation and migration of Hep3B and HCCLM3 cells in a concentration-dependent manner. RNA-sequencing showed that 77 genes are upregulated and 136 genes are downregulated in STA-treated cells compared with untreated cells. KEGG pathway analysis showed significant enrichment in galactose metabolism as well as in fructose and mannose metabolism. Further gas chromatography-mass spectrometric analysis (GC-MS) confirmed this, indicating that STA significantly inhibits the glucose metabolism pathway of Hep3B cells. Tumor xenograft in nude mice showed that STA has a significant inhibitory effect on tumor growth . In conclusion, our results indicate that STA can inhibit cell proliferation by regulating glucose metabolism, with subsequent anti-tumor effects, and has the potential to be a candidate drug for the treatment of liver cancer.

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References

Hagenbuchner J, Kiechl-Kohlendorfer U, Obexer P, Ausserlechner M . BIRC5/Survivin as a target for glycolysis inhibition in high-stage neuroblastoma. Oncogene. 2015; 35(16):2052-61. DOI: 10.1038/onc.2015.264. View

Li X, Yang Y, Zhang B, Lin X, Fu X, An Y . Lactate metabolism in human health and disease. Signal Transduct Target Ther. 2022; 7(1):305. PMC: 9434547. DOI: 10.1038/s41392-022-01151-3. View

Guo Y, Li X, Sun X, Wang J, Yang X, Zhou X . Combined Aberrant Expression of NDRG2 and LDHA Predicts Hepatocellular Carcinoma Prognosis and Mediates the Anti-tumor Effect of Gemcitabine. Int J Biol Sci. 2019; 15(9):1771-1786. PMC: 6743297. DOI: 10.7150/ijbs.35094. View

Qu L, Wang C, Xu H, Li L, Liu Y, Wan Q . Atractylodin targets GLA to regulate D-mannose metabolism to inhibit osteogenic differentiation of human valve interstitial cells and ameliorate aortic valve calcification. Phytother Res. 2022; 37(2):477-489. DOI: 10.1002/ptr.7628. View

Qi S, Deng S, Lian Z, Yu K . Novel Drugs with High Efficacy against Tumor Angiogenesis. Int J Mol Sci. 2022; 23(13). PMC: 9267017. DOI: 10.3390/ijms23136934. View

Tan Y, Li J, Zhao G, Huang K, Cardenas H, Wang Y . Metabolic reprogramming from glycolysis to fatty acid uptake and beta-oxidation in platinum-resistant cancer cells. Nat Commun. 2022; 13(1):4554. PMC: 9356138. DOI: 10.1038/s41467-022-32101-w. View

Gui Y, Yang Y, Xu D, Tao S, Li J . Schisantherin A attenuates sepsis-induced acute kidney injury by suppressing inflammation via regulating the NRF2 pathway. Life Sci. 2020; 258:118161. DOI: 10.1016/j.lfs.2020.118161. View

Zhang X, Li Y, Ma Y, Yang L, Wang T, Meng X . Yes-associated protein (YAP) binds to HIF-1α and sustains HIF-1α protein stability to promote hepatocellular carcinoma cell glycolysis under hypoxic stress. J Exp Clin Cancer Res. 2018; 37(1):216. PMC: 6123950. DOI: 10.1186/s13046-018-0892-2. View

Pan L, Feng F, Wu J, Fan S, Han J, Wang S . Demethylzeylasteral targets lactate by inhibiting histone lactylation to suppress the tumorigenicity of liver cancer stem cells. Pharmacol Res. 2022; 181:106270. DOI: 10.1016/j.phrs.2022.106270. View

10.

Jiang Y, Fan X, Wang Y, Tan H, Chen P, Zeng H . Hepato-protective effects of six schisandra lignans on acetaminophen-induced liver injury are partially associated with the inhibition of CYP-mediated bioactivation. Chem Biol Interact. 2015; 231:83-9. DOI: 10.1016/j.cbi.2015.02.022. View

11.

Yalcin A, Clem B, Imbert-Fernandez Y, Ozcan S, Peker S, ONeal J . 6-Phosphofructo-2-kinase (PFKFB3) promotes cell cycle progression and suppresses apoptosis via Cdk1-mediated phosphorylation of p27. Cell Death Dis. 2014; 5:e1337. PMC: 4123086. DOI: 10.1038/cddis.2014.292. View

12.

Li S, Li J, Dai W, Zhang Q, Feng J, Wu L . Genistein suppresses aerobic glycolysis and induces hepatocellular carcinoma cell death. Br J Cancer. 2017; 117(10):1518-1528. PMC: 5680469. DOI: 10.1038/bjc.2017.323. View

13.

Woo C, Chen W, Teo X, Radda G, Lee P . Downregulating serine hydroxymethyltransferase 2 (SHMT2) suppresses tumorigenesis in human hepatocellular carcinoma. Oncotarget. 2016; 7(33):53005-53017. PMC: 5288164. DOI: 10.18632/oncotarget.10415. View

14.

Wen Q, Chan K, Shi K, Lv J, Guo Y, Pei P . Tobacco smoking and solid fuels for cooking and risk of liver cancer: A prospective cohort study of 0.5 million Chinese adults. Int J Cancer. 2022; 151(2):181-190. PMC: 7612779. DOI: 10.1002/ijc.33977. View

15.

DeBerardinis R, Keshari K . Metabolic analysis as a driver for discovery, diagnosis, and therapy. Cell. 2022; 185(15):2678-2689. PMC: 9469798. DOI: 10.1016/j.cell.2022.06.029. View

16.

Fan Y, Ma Z, Zhao L, Wang W, Gao M, Jia X . Anti-tumor activities and mechanisms of Traditional Chinese medicines formulas: A review. Biomed Pharmacother. 2020; 132:110820. DOI: 10.1016/j.biopha.2020.110820. View

17.

Sheng T, Mao X, Zhang S . CaMKKβ regulates proliferation, apoptosis, and glycolysis of hepatocellular carcinoma via PI3K/AKT pathway. Ann Palliat Med. 2020; 9(6):3857-3869. DOI: 10.21037/apm-20-1789. View

18.

Faloppi L, Bianconi M, Memeo R, Casadei Gardini A, Giampieri R, Bittoni A . Lactate Dehydrogenase in Hepatocellular Carcinoma: Something Old, Something New. Biomed Res Int. 2016; 2016:7196280. PMC: 4903134. DOI: 10.1155/2016/7196280. View

19.

Sacco R, Tapete G, Simonetti N, Sellitri R, Natali V, Melissari S . Transarterial chemoembolization for the treatment of hepatocellular carcinoma: a review. J Hepatocell Carcinoma. 2017; 4:105-110. PMC: 5538681. DOI: 10.2147/JHC.S103661. View

20.

Thadathil N, Selvarani R, Mohammed S, Nicklas E, Tran A, Kamal M . Senolytic treatment reduces cell senescence and necroptosis in Sod1 knockout mice that is associated with reduced inflammation and hepatocellular carcinoma. Aging Cell. 2022; 21(8):e13676. PMC: 9381894. DOI: 10.1111/acel.13676. View