Derivate Isocorydine (d-ICD) Suppresses Migration and Invasion of Hepatocellular Carcinoma Cell by Downregulating ITGA1 Expression

Liu, Xiaoqin; Tian, Hua; Li, Hong; Ge, Chao; Zhao, Fangyu; Yao, Ming; Li, Jinjun

doi:10.3390/ijms18030514

Cited by 25 publications

(16 citation statements)

References 34 publications

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“…The role of integrin α1 in HCC metastasis is currently unclear. Liu et al (25) detected a positive correlation between integrin α1 and migration and invasion, which is in accordance with the present study. However, compared with the present investigation, adhesion assays were not conducted.…”

Section: Suppression Of Adhesion By Everolimus and Temsirolimussupporting

confidence: 93%

mTOR inhibition reduces growth and adhesion of hepatocellular carcinoma cells in vitro

Engl

Rutz

Maxeiner

et al. 2017

Molecular Medicine Reports

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Mechanistic target of rapamycin (mTOR) signaling is typically increased in hepatocellular carcinoma (HCC). A panel of HCC cell lines (HepG2, Hep3B and HuH6) was exposed to various concentrations of the mTOR inhibitors, everolimus and temsirolimus, in order to investigate their effects on cell growth, clonal formation, cell cycle progression, and adhesion and chemotactic migration using MTT and clonal cell growth assays, fluorometric detection of cell cycle phases and a Boyden chamber assay. In addition, integrin α and β adhesion receptors were analyzed by flow cytometry and blocking studies using function blocking monoclonal antibodies were conducted to explore functional relevance. The results demonstrated that everolimus and temsirolimus significantly suppressed HCC cell growth and clonal formation, at 0.1 or 1 nM (depending on the cell line). In addition, the number of cells in G0/G1 phase was increased in response to drug treatment, whereas the number of G2/M phase cells was decreased. Drug treatment also considerably suppressed HCC cell adhesion to immobilized collagen. Integrin profiling revealed strong expression of integrin α1, α2, α6 and β1 subtypes; and integrin α1 was upregulated in response to mTOR inhibition. Suppression of integrin α1 did not affect cell growth; however, it did significantly decrease adhesion and chemotaxis, with the influence on adhesion being greater than that on motility. Due to a positive association between integrin α1 expression and the extent of adhesion, whereby reduced receptor expression was correlated to decreased cell adhesion, it may be hypothesized that the adhesion‑blocking effects of mTOR inhibitors are not associated with mechanical contact inhibition of the α1 receptor but with integrin α1‑dependent suppression of oncogenic signaling, thus preventing tumor cell‑matrix interaction.

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Section: Suppression Of Adhesion By Everolimus and Temsirolimussupporting

confidence: 93%

mTOR inhibition reduces growth and adhesion of hepatocellular carcinoma cells in vitro

Engl

Rutz

Maxeiner

et al. 2017

Molecular Medicine Reports

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“…The identification of ITGA1 was involved in cell invasion and metastasis in hepatocellular carcinomas [27]. In our study, we demonstrated that ITGA1 was highly expressed in CRC tumors.…”

Section: Discussionsupporting

confidence: 54%

Integrin α1 promotes tumorigenicity and progressive capacity of colorectal cancer

Li¹,

Wang²,

Rong³

et al. 2020

Int. J. Biol. Sci.

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Colorectal cancer (CRC) is the second leading cause of death globally. Integrin α1 (ITGA1) belongs to integrin family and involves in regulating cell adhesion, invasion, proliferation and tumorigenicity, its expression is up-regulated in various cancers, including CRC. However, the molecular understanding and clinical relevance of ITGA1 in the development and progression of CRC remain unclear. In the present study, we detected ITGA1 in 50 CRC tissues and adjacent non-cancerous tissues, sera from 100 CRC patients and 50 healthy subjects, and four CRC cell lines using immunohistochemistry staining, enzyme-linked immunosorbent assay and Western blotting. We found that the ITGA1 protein was significantly higher in human CRC tissues and cell lines than both paired non-tumor tissues and normal cells, respectively. In addition, the serum concentration of ITGA1 was also higher in CRC patients compared to the healthy subjects (p<0.01) and was significantly associated with metastatic TNM stages (p<0.0001) and circulating carbohydrate antigen 199 (CA199) (p<0.022). Furthermore, down-regulation of ITGA1 with transfecting LV-shITGA1 inhibited the progressive capacity of cell migration and invasion in CRC SW480 cell line and the tumorgenicity in nude mice. In functional studies, ITGA1 knockdown also inhibited Ras/ERK signaling pathway by decreasing the expression of Ras, p-Erk1/2 and c-Myc in SW480. Contrastly, when evelated expression of ITGA1 in NCM460 coincided with the increased expression of Ras, p-Erk1/2 and c-Myc. Taken together, our findings suggest that ITGA1 is an oncogene with a capability to promote CRC cell migration, invasion and tumorigenicity by activating the Ras/Erk signaling, implying that it may be a novel target for the diagnosis and treatment of CRC, and warrants further investigation.

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“…Palmatine (PMT) has been confirmed to possess antibacterial, antifungal, antivirus and anti‐inflammatory activities in vitro and in vivo (Chao et al, ; Kim et al, ; Kong, Zhao, Xiao, Li, & Ren, ; Singh & Kakkar, ; Yan, Jin, Xiao, & Dong, ). The anticancer activities of isocorydine (ICD) and its derivatives have been investigated for cytotoxicity and their interaction with DNA and topoisomerases (Hoet et al, ), also supported by our work (Chen et al, ; Li et al, ; Liu et al, ; Lu et al, ; Sun et al, ; Yan et al, ; Zhong et al, ). ICD also has potential antiviral and antiparasitic activities (Montenegro et al, ).…”

Section: Introductionsupporting

confidence: 69%

Development of an HPLC‐DAD method for the determination of five alkaloids in Stephania yunnanensis Lo and in rat plasma after oral dose of Stephania yunnanensis Lo extracts

Xin

Zhang

et al. 2018

Biomedical Chromatography

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For the rational utilization and the quantitative quality control of the Stephania yunnanensis Lo, an HPLC-DAD method was developed for the quantitative and simultaneous determination of five alkaloids in rat plasma (stepharine, sinomenine, palmatine, isocorydine and tetrahydropalmatine), which were the main active chemical constituents of this plant and belong to four kinds of isoquinoline-type alkaloids (protoberberine, morphine, aporphine and protaporphine alkaloids). The contents of five alkaloids ranged from 0.09 to 2.32% (w/w). The method validation was tested for the linearity (r > 0.9975), precision (intra-day RSD < 4.8% and inter-day RSD < 4.9%), extraction recovery (85.49 ± 2.29% to 99.21 ± 1.48%) and stability (98.5 ± 5.3% to 101.2 ± 3.4%). We developed an HPLC-DAD method to simultaneously measure these alkaloids in rat plasma after oral administration of the extract of this plant to rats. The results supported the hypothesis that isoquinoline alkaloids were the compounds responsible for the main pharmacological activities for anti-inflammatory and analgesic.

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Derivate Isocorydine (d-ICD) Suppresses Migration and Invasion of Hepatocellular Carcinoma Cell by Downregulating ITGA1 Expression

Cited by 25 publications

References 34 publications

mTOR inhibition reduces growth and adhesion of hepatocellular carcinoma cells in vitro

mTOR inhibition reduces growth and adhesion of hepatocellular carcinoma cells in vitro

Integrin α1 promotes tumorigenicity and progressive capacity of colorectal cancer

Development of an HPLC‐DAD method for the determination of five alkaloids in Stephania yunnanensis Lo and in rat plasma after oral dose of Stephania yunnanensis Lo extracts

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