Chlorogenic acid effectively treats cancers through induction of cancer cell differentiation

Huang, Shuai; Wang, Lu-Lu; Xue, Ni-Na; Li, Cong; Guo, Hui-Hui; Ren, Tian-Kun; Zhan, Yun; Li, Wen-Bing; Zhang, Jie; Chen, Xiao-Guang; Han, Yan-Xing; Zhang, Jin-Lan; Jiang, Jian-Dong

doi:10.7150/thno.34674



Nanotheranostics 2024; 8(4): 442-457. [Abstract] [Full text] [PDF]

Nanotheranostics 2024; 8(4): 427-441. [Abstract] [Full text] [PDF]

Nanotheranostics

International Journal of Biological Sciences

International Journal of Medical Sciences

Journal of Cancer

Global reach, higher impact

Full Text | PDF

Theranostics 2019; 9(23):6745-6763. doi:10.7150/thno.34674 This issue Cite

Research Paper

Chlorogenic acid effectively treats cancers through induction of cancer cell differentiation

Shuai Huang^1,4*, Lu-Lu Wang^1*, Ni-Na Xue¹, Cong Li¹, Hui-Hui Guo¹, Tian-Kun Ren¹, Yun Zhan¹, Wen-Bing Li², Jie Zhang³, Xiao-Guang Chen¹, Yan-Xing Han^1✉, Jin-Lan Zhang^1✉, Jian-Dong Jiang^1,4✉

1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China
2. Department of Glioma, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
3. Jiuzhang Biochemical Engineering Science and Technology Development Co., Ltd, Chengdu, Sichuan, 610041, China
4. Laboratory of Antiviral Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China
^*Equal contribution to the work.

Citation:

Huang S, Wang LL, Xue NN, Li C, Guo HH, Ren TK, Zhan Y, Li WB, Zhang J, Chen XG, Han YX, Zhang JL, Jiang JD. Chlorogenic acid effectively treats cancers through induction of cancer cell differentiation. Theranostics 2019; 9(23):6745-6763. doi:10.7150/thno.34674. https://www.thno.org/v09p6745.htm

Other styles

Abstract

Rationale: Inducing cancer differentiation is a promising approach to treat cancer. Here, we identified chlorogenic acid (CA), a potential differentiation inducer, for cancer therapy, and elucidated the molecular mechanisms underlying its differentiation-inducing effects on cancer cells.

Methods: Cancer cell differentiation was investigated by measuring malignant behavior, including growth rate, invasion/migration, morphological change, maturation, and ATP production. Gene expression was analyzed by microarray analysis, qRT-PCR, and protein measurement, and molecular biology techniques were employed for mechanistic studies. LC/MS analysis was the method of choice for chemical detection. Finally, the anticancer effect of CA was evaluated both in vitro and in vivo.

Results: Cancer cells treated with CA showed reduced proliferation rate, migration/invasion ability, and mitochondrial ATP production. Treating cancer cells with CA resulted in elevated SUMO1 expression through acting on its 3'UTR and stabilizing the mRNA. The increased SUMO1 caused c-Myc sumoylation, miR-17 family downregulation, and p21 upregulation leading to G₀/G₁ arrest and maturation phenotype. CA altered the expression of differentiation-related genes in cancer cells but not in normal cells. It inhibited hepatoma and lung cancer growth in tumor-bearing mice and prevented new tumor development in naïve mice. In glioma cells, CA increased expression of specific differentiation biomarkers Tuj1 and GFAP inducing differentiation and reducing sphere formation. The therapeutic efficacy of CA in glioma cells was comparable to that of temozolomide. CA was detectable both in the blood and brain when administered intraperitoneally in animals. Most importantly, CA was safe even at very high doses.

Conclusion: CA might be a safe and effective differentiation-inducer for cancer therapy. “Educating” cancer cells to differentiate, rather than killing them, could be a novel therapeutic strategy for cancer.

Keywords: chlorogenic acid, cancer differentiation, SUMO1, c-Myc, p21

Citation styles

APA

Huang, S., Wang, L.L., Xue, N.N., Li, C., Guo, H.H., Ren, T.K., Zhan, Y., Li, W.B., Zhang, J., Chen, X.G., Han, Y.X., Zhang, J.L., Jiang, J.D. (2019). Chlorogenic acid effectively treats cancers through induction of cancer cell differentiation. Theranostics, 9(23), 6745-6763. https://doi.org/10.7150/thno.34674.

ACS

Huang, S.; Wang, L.L.; Xue, N.N.; Li, C.; Guo, H.H.; Ren, T.K.; Zhan, Y.; Li, W.B.; Zhang, J.; Chen, X.G.; Han, Y.X.; Zhang, J.L.; Jiang, J.D. Chlorogenic acid effectively treats cancers through induction of cancer cell differentiation. Theranostics 2019, 9 (23), 6745-6763. DOI: 10.7150/thno.34674.

NLM

CSE

Huang S, Wang LL, Xue NN, Li C, Guo HH, Ren TK, Zhan Y, Li WB, Zhang J, Chen XG, Han YX, Zhang JL, Jiang JD. 2019. Chlorogenic acid effectively treats cancers through induction of cancer cell differentiation. Theranostics. 9(23):6745-6763.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.