2. Academic Validation
  3. Chlorogenic acid effectively treats cancers through induction of cancer cell differentiation

Chlorogenic acid effectively treats cancers through induction of cancer cell differentiation

  • Theranostics. 2019 Sep 19;9(23):6745-6763. doi: 10.7150/thno.34674.
Shuai Huang 1 2,  Lu-Lu Wang 1,  Ni-Na Xue 1,  Cong Li 1,  Hui-Hui Guo 1,  Tian-Kun Ren 1,  Yun Zhan 1,  Wen-Bing Li 3,  Jie Zhang 4,  Xiao-Guang Chen 1,  Yan-Xing Han 1,  Jin-Lan Zhang 1,  Jian-Dong Jiang 1 2
Affiliations

Affiliations

  • 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 Laboratory of Antiviral Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
  • 3 Department of Glioma, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.
  • 4 Jiuzhang Biochemical Engineering Science and Technology Development Co., Ltd, Chengdu, Sichuan, 610041, China.
PMID: 31660066 DOI: 10.7150/thno.34674
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

SUMO1; c-Myc; cancer differentiation; chlorogenic acid; p21.

Figures
Products