Traditional Chinese medicine Kuan-Sin-Yin decoction inhibits cell mobility via downregulation of CCL2, CEACAM1 and PIK3R3 in hepatocellular carcinoma cells

Chueh-Tan Chen; Chian-Feng Chen; Tung-Yi Lin; Wei-Jyun Hua; Kate Hua; Ching-Yao Tsai; Chung-Hua Hsu

doi:10.1016/j.jep.2023.116834

Traditional Chinese medicine Kuan-Sin-Yin decoction inhibits cell mobility via downregulation of CCL2, CEACAM1 and PIK3R3 in hepatocellular carcinoma cells

J Ethnopharmacol. 2023 Dec 5:317:116834. doi: 10.1016/j.jep.2023.116834. Epub 2023 Jun 22.

Authors

Chueh-Tan Chen¹, Chian-Feng Chen², Tung-Yi Lin³, Wei-Jyun Hua⁴, Kate Hua⁵, Ching-Yao Tsai⁶, Chung-Hua Hsu⁷

Affiliations

¹ Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: chuehtan@hotmail.com.
² Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: cfchen@nycu.edu.tw.
³ Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Program in Molecular Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: biotungyi@gmail.com.
⁴ Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Program in Molecular Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: karta603.ls09@nycu.edu.tw.
⁵ Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: katehua@nycu.edu.tw.
⁶ Department of Ophthalmology, Taipei City Hospital, Taipei, Taiwan; Institute of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Business Administration, Fu Jen Catholic University, New Taipei, Taiwan; General Education Center, University of Taipei, Taipei, Taiwan. Electronic address: ayitgroup@gmail.com.
⁷ Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Chinese Medicine, Taipei City Hospital, Linsen, Chinese Medicine, and Kunming Branch, Taipei, Taiwan. Electronic address: chhsu@nycu.edu.tw.

PMID: 37355084
DOI: 10.1016/j.jep.2023.116834

Abstract

Ethnopharmacological relevance: Kuan-Sin-Yin (KSY) is a traditional Chinese medical decoction, designed based on the classic Si-Jun-Zi-Tang decoction and used clinically to improve the synergic effects of energy promotion, liver function and cancer related symptom and quality of life. However, the anti-hepatocellular carcinoma (HCC) function of KSY is unclear.

Aim of the study: This study aimed to investigate the anti-mobility activity of KSY on HCC cells and elucidate its molecular mechanism.

Materials and methods: Two malignancy hepatocellular carcinoma cells, Mahlavu and SK-Hep-1, were used for the test of cell proliferation via alarm blue assay. The wound healing and Transwell assays were used to determine the anti-mobility activity of KSY in HCC cells. Cell morphology was analyzed via confocal microscopy. The genomic profile of KSY-treated HCC cells was analyzed by microarray. The potential signaling pathways and bio-functions of KSY-mediated genes were analyzed by ingenuity pathway analysis (IPA). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the messenger RNA (mRNA) level of indicated gene.

Results: KSY did not affect cell viability of HCC cells but significantly inhibited cell migration and invasion in those HCC Mahlavu and SK-Hep-1 cells. In parallel, KSY induced changes in morphology of HCC cells via re-modulating actin cytoskeleton. KSY upregulated 1270 genes but reduced 1534 genes in Mahlavu cells. KSY regulated various gene networks which controlled cell migration, invasion and movement. Specifically, KSY reduced expression of chemokine (C-C motif) ligand 2 (CCL2), which is correlated to cell mobility, and concomitantly downregulated mRNA levels of phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) and CEA cell adhesion molecule 1 (CEACAM1).

Conclusion: These findings indicated that regulation of CCL2-mediated PIK3R3 and CEACAM1 may be involved in KSY inhibited cell mobility. Moreover, KSY may be a potential a Chinese decoction for reducing cell mobility.

Keywords: Cell motility; Chemokine (C-C motif) ligand 2; Hepatocellular carcinoma; Kuan-Sin-Yin.

MeSH terms

Carcinoma, Hepatocellular* / drug therapy
Carcinoma, Hepatocellular* / genetics
Carcinoma, Hepatocellular* / pathology
Cell Line, Tumor
Cell Movement
Cell Proliferation
Chemokine CCL2 / metabolism
Down-Regulation
Gene Expression Regulation, Neoplastic
Humans
Liver Neoplasms* / drug therapy
Liver Neoplasms* / genetics
Liver Neoplasms* / metabolism
Medicine, Chinese Traditional
Phosphatidylinositol 3-Kinases / metabolism
Quality of Life

Substances

CD66 antigens
CCL2 protein, human
Chemokine CCL2
PIK3R3 protein, human
Phosphatidylinositol 3-Kinases