Unknown

Dataset Information

0

Chlorogenic acid effectively treats cancers through induction of cancer cell differentiation.


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.

SUBMITTER: Huang S 

PROVIDER: S-EPMC6815948 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

altmetric image

Publications

Chlorogenic acid effectively treats cancers through induction of cancer cell differentiation.

Huang Shuai S   Wang Lu-Lu LL   Xue Ni-Na NN   Li Cong C   Guo Hui-Hui HH   Ren Tian-Kun TK   Zhan Yun Y   Li Wen-Bing WB   Zhang Jie J   Chen Xiao-Guang XG   Han Yan-Xing YX   Zhang Jin-Lan JL   Jiang Jian-Dong JD  

Theranostics 20190919 23


<h4>Rationale</h4>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.<h4>Methods</h4>Cancer cell differentiation was investigated by measuring malignant behavior, including growth rate, invasion/migration, morphological change, maturation, and ATP production. Gene expressio  ...[more]

Similar Datasets

| S-EPMC6681197 | biostudies-literature
| S-EPMC16575 | biostudies-literature
| S-EPMC8286308 | biostudies-literature
| S-EPMC10421662 | biostudies-literature
| S-EPMC5900968 | biostudies-literature
| S-EPMC10589730 | biostudies-literature
| S-EPMC5568550 | biostudies-literature
| S-EPMC6073821 | biostudies-literature
| S-EPMC7248290 | biostudies-literature
| S-EPMC5206721 | biostudies-literature