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Recent Patents on Anti-Cancer Drug Discovery

Editor-in-Chief

ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

Research Article

Chlorogenic Acid Inhibits Proliferation, Migration and Invasion of Pancreatic Cancer Cells via AKT/GSK-3β/β-catenin Signaling Pathway

Author(s): Xiaoliang Chen, Binyu Liu, Jiale Tong, Jianing Bo, Miao Feng, Lili Yin* and Xiukun Lin*

Volume 19, Issue 2, 2024

Published on: 20 April, 2023

Page: [146 - 153] Pages: 8

DOI: 10.2174/1574892818666230327134746

Price: $65

Abstract

Background: Chlorogenic acid (CA, United States Patent No. 10772340), a natural biologically active food ingredient, displays potent antitumor activity against a variety of cancer cells. However, the mechanism underlying its anticancer effect is not well elucidated.

Objective: In the present study, we hope to dissect the mechanism underlying the anticancer effects of CA in pancreatic cancer cells.

Methods: The cytotoxicity of CA in pancreatic cancer cells was determined by MTT assay. Flow cytometry was performed to evaluate the cells apoptosis, while a clonogenic assay was carried out to check the colony formation of cancer cells. Transwell assay was performed to assess the cells migration and invasion. The protein expression of AKT/GSK-3β/β-catenin signaling pathway was detected by Western Blot.

Results: Our data indicated that CA inhibited the proliferation of PANC-28 and PANC-1 cells in a dose and time-dependent manner. CA was able to inhibit colony formation, migration, and invasion ability and trigger apoptosis in PANC-28 and PANC-1 cells. Further study showed that CA down-regulated the expression of AKT, p-AKT(Thr308), p-GSK-3β(Ser9), β-catenin, N-cadherin, and vimentin while enhancing the expression of cleaved-caspase 3 and cleaved-caspase 7 in PANC-28 and PANC-1 cells.

Conclusion: Our study provides significant evidence that CA is able to inhibit the growth of pancreatic cancer via the AKT/GSK-3β/β-catenin signaling pathway.

[1]
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin 2021; 71(1): 7-33.
[http://dx.doi.org/10.3322/caac.21654] [PMID: 33433946]
[2]
Sapio L, Salzillo A, Illiano M, et al. Chlorogenic acid activates ERK1/2 and inhibits proliferation of osteosarcoma cells. J Cell Physiol 2020; 235(4): 3741-52.
[http://dx.doi.org/10.1002/jcp.29269] [PMID: 31602671]
[3]
Wang L, Du H, Chen P. Chlorogenic acid inhibits the proliferation of human lung cancer A549 cell lines by targeting annexin A2 in vitro and in vivo. Biomed Pharmacother 2020; 131: 110673.
[http://dx.doi.org/10.1016/j.biopha.2020.110673] [PMID: 32882585]
[4]
Zeng A, Liang X, Zhu S, et al. Chlorogenic acid induces apoptosis, inhibits metastasis and improves antitumor immunity in breast cancer via the NF κB signaling pathway. Oncol Rep 2020; 45(2): 717-27.
[http://dx.doi.org/10.3892/or.2020.7891] [PMID: 33416150]
[5]
Hou N, Liu N, Han J, Yan Y, Li J. Chlorogenic acid induces reactive oxygen species generation and inhibits the viability of human colon cancer cells. Anticancer Drugs 2017; 28(1): 59-65.
[http://dx.doi.org/10.1097/CAD.0000000000000430] [PMID: 27603595]
[6]
Liu Y, Feng Y, Li Y, et al. Chlorogenic acid decreases malignant characteristics of hepatocellular carcinoma cells by inhibiting DNMT1 expression. Front Pharmacol 2020; 11: 867-7.
[http://dx.doi.org/10.3389/fphar.2020.00867] [PMID: 32655395]
[7]
Lu CH, Chen WT, Hsieh CH, Kuo YY, Chao CY. Thermal cycling-hyperthermia in combination with polyphenols, epigallocatechin gallate and chlorogenic acid, exerts synergistic anticancer effect against human pancreatic cancer PANC-1 cells. PLoS One 2019; 14(5): e0217676.
[http://dx.doi.org/10.1371/journal.pone.0217676] [PMID: 31150487]
[8]
Chen X, Xu H, Wu N, et al. Interaction between granulin A and enolase 1 attenuates the migration and invasion of human hepatoma cells. Oncotarget 2017; 8(18): 30305-16.
[http://dx.doi.org/10.18632/oncotarget.16328] [PMID: 28415822]
[9]
Chen X, Yin L, Qiao G, et al. Inhibition of Rac1 reverses enzalutamide resistance in castration resistant prostate cancer. Oncol Lett 2020; 20(3): 2997-3005.
[http://dx.doi.org/10.3892/ol.2020.11823] [PMID: 32782617]
[10]
Chen YJ, Li Y, Guo X, et al. Upregulation of IRF9 Contributes to pulmonary artery smooth muscle cell proliferation during pulmonary arterial hypertension. Front Pharmacol 2021; 12: 773235-5.
[http://dx.doi.org/10.3389/fphar.2021.773235] [PMID: 34925032]
[11]
Song M, Bode AM, Dong Z, Lee MH. AKT as a therapeutic target for cancer. Cancer Res 2019; 79(6): 1019-31.
[http://dx.doi.org/10.1158/0008-5472.CAN-18-2738] [PMID: 30808672]
[12]
Sebti SM. Substrate-mimetic Akt inhibitor. In. Edited by University of South Florida (Tampa F, US),Yale University (New Haven, CT, US). Patent no. 9453049, United States, 2016.
[13]
Deng X. Inhibitors of Mcl-1 and Akt binding, pharmaceutical compositions, and uses in treating cancer. In. Edited by Emory University (Atlanta, GA, US). US Patent no. 20210137953, 2021.
[14]
Huang P, Yan R, Zhang X, Wang L, Ke X, Qu Y. Activating Wnt/β-catenin signaling pathway for disease therapy: Challenges and opportunities. Pharmacol Ther 2019; 196: 79-90.
[http://dx.doi.org/10.1016/j.pharmthera.2018.11.008] [PMID: 30468742]
[15]
Shang S, Hua F, Hu ZW. The regulation of β-catenin activity and function in cancer: Therapeutic opportunities. Oncotarget 2017; 8(20): 33972-89.
[http://dx.doi.org/10.18632/oncotarget.15687] [PMID: 28430641]
[16]
Wang X, Liu J, Xie Z, et al. Chlorogenic acid inhibits proliferation and induces apoptosis in A498 human kidney cancer cells via inactivating PI3K/Akt/mTOR signalling pathway. J Pharm Pharmacol 2019; 71(7): 1100-9.
[http://dx.doi.org/10.1111/jphp.13095] [PMID: 30989669]
[17]
Changizi Z, Moslehi A, Rohani AH, Eidi A. Chlorogenic acid induces 4T1 breast cancer tumor’s apoptosis via p53, Bax, Bcl‐2, and caspase‐3 signaling pathways in BALB/c mice. J Biochem Mol Toxicol 2021; 35(2): e22642.
[http://dx.doi.org/10.1002/jbt.22642] [PMID: 33058431]
[18]
Changizi Z, Moslehi A, Rohani A, Eidi A. Chlorogenic acid inhibits growth of 4T1 breast cancer cells through involvement in Bax/Bcl2 pathway. J Cancer Res and Ther 2020; 16(6): 1435-42.
[http://dx.doi.org/10.4103/jcrt.JCRT_245_19] [PMID: 33342809]
[19]
Ma Y, Di Y, Li Q, et al. LncRNAs as epigenetic regulators of epithelial to mesenchymal transition in pancreatic cancer. Discover Oncology 2022; 13(1): 61.
[http://dx.doi.org/10.1007/s12672-022-00522-0] [PMID: 35819532]
[20]
Wang L, Heidt DG, Lee CJ, et al. Oncogenic function of ATDC in pancreatic cancer through Wnt pathway activation and β-catenin stabilization. Cancer Cell 2009; 15(3): 207-19.
[http://dx.doi.org/10.1016/j.ccr.2009.01.018] [PMID: 19249679]
[21]
Chen LJ, Wu L, Wang W, et al. Long non coding RNA 01614 hyperactivates WNT/β catenin signaling to promote pancreatic cancer progression by suppressing GSK 3β. Int J Oncol 2022; 61(4): 116.
[http://dx.doi.org/10.3892/ijo.2022.5406] [PMID: 35929518]

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