F-Actin Reorganization and Inactivation of Rho Signaling Pathway Involved in the Inhibitory Effect of Coptidis Rhizoma on Hepatoma Cell Migration

Wang, Ning; Feng, Yibin; Lau, Echo Ping Woi; Tsang, Chi-Man; Ching, Yick–Pang; Kwan, Chiman; Tong, Yao; Nagamatsu, Tadashi; Sui, Weiwei; Tsao, Sai‐Wah

doi:10.1177/1534735410379121

Cited by 48 publications

(23 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is the fifth common malignant tumor in men while seventh common in women [1], and it is the third common causes of cancer mortality all over the world with the incidence rates are increasing every year [3]. Although currently different therapeutic strategies have developed, the prognosis of HCC remains poor due to the high reoccurrence rate and metastatic effect of HCC cells [4]. Incidence of intrahepatic metastatic is high in hepatocellular carcinoma with infiltrate growth pattern according to clinicopathologic study [5].…”

Section: Introductionmentioning

confidence: 99%

Up-Regulation of TIMP-1 by Genipin Inhibits MMP-2 Activities and Suppresses the Metastatic Potential of Human Hepatocellular Carcinoma

et al. 2012

View full text Add to dashboard Cite

Aim of the StudyHepatocellular carcinoma is one of the most malignant human cancers with high metastatic potential. The aim of this study is to investigate the anti-metastatic effect of genipin and its underlying mechanism.Experimental ApproachThe anti-metastatic potential of genipin was evaluated by both cell and animal model. Wound healing and invasion chamber assays were introduced to examine the anti-migration and anti-invasion action of genipin in human hepatocellular carcinoma cell HepG2 and MHCC97L; orthotopical implantation model was used for in vivo evaluation. Gelatin Zymography, Immunoblotting, quantitative real-time polymerase chain reaction and ELISA assays were used to study the mechanisms underlying genipin’s anti-metastatic effect.Key ResultsGenipin suppresses the motility and invasiveness of HepG2 and MHCC97L at non-toxic doses, which may be correlated to the inhibition of genipin on MMP-2 activities in the cells. No significant reduced expression of MMP-2 was observed either at mRNA or at protein level. Furthermore, genipin could specifically up-regulate the expression of TIMP-1, the endogenous inhibitor of MMP-2 activities. Silencing of TIMP-1 by RNA interference abolishes genipin’s anti-metastaic effect. Activation of p38 MAPK signaling was observed in genipin-treated cells, which is responsible for the TIMP-1 overexpression and MMP-2 inhibition. Presence of SB202190, the p38 MAPK inhibitor, attenuates the anti-metastatic potential of genipin in hepatocellular carcinoma. Orthotopical implantation model showed that genipin could suppress the intrahepatic metastatic as well as tumor expansion in liver without exhibiting potent toxicity.ConclusionOur findings demonstrated the potential of genipin in suppressing hepatocellular carcinoma metastasis, and p38/TIMP-1/MMP-2 pathway may be involved as the key mechanism of its anti-metastasis effect.

show abstract

Section: Introductionmentioning

confidence: 99%

Up-Regulation of TIMP-1 by Genipin Inhibits MMP-2 Activities and Suppresses the Metastatic Potential of Human Hepatocellular Carcinoma

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Among heatclearing herbs, Coptidis Rhizoma (Huang Lian) may reduce Factin polymerization and damage to cytoskeleton network to inhibit hepatocarcinoma cell migration [159] . Baicalein, a compound from Scutellaria baicalensis Georgi (HuangQin), could inhibit migration and invasion in human hepatocellular carcinoma SMMC 7721 cells accompanied by downregulation of ezrin, VEGF, and MMP9 [160] .…”

Section: Inhibition Of Metastasismentioning

confidence: 99%

Traditional Chinese medicine for prevention and treatment of hepatocarcinoma: From bench to bedside

Wang

2015

WJH

View full text Add to dashboard Cite

and other TCM syndromes (Zheng). Modern treatments such as surgery, transarterial chemoembolization (TACE) and high intensity focus ultrasound treatment would influence the manifestation of TCM syndromes. Herbs with traditional efficacy of tonifying Qi, blood and Yin, soothing liver-Qi stagnation, clearing heat and detoxifying and dissolving stasis, have been demonstrated to be potent to prevent hepatocarcinogenesis. TCM has been widely used in all aspects of integrative therapy in hepatocarcinoma, including surgical resection, liver transplantation, TACE, local ablative therapies and even as monotherapy for middle-advanced stage hepatocarcinoma. Clinical practices have confirmed that TCM is effective to alleviate clinical symptoms, improve quality of life and immune function, prevent recurrence and metastasis, delay tumor progression, and prolong survival time in hepatocarcinoma patients. The effective mechanism of TCM against hepatocarcinoma is related to inducing apoptosis, autophagy, anoikis and cell senescence, arresting cell cycle, regulating immune function, inhibiting metastasis and angiogenesis, reversing drug resistance and enhancing effects of chemotherapy. Along with the progress of research in this field, TCM will contribute more to the prevention and treatment of hepatocarcinoma. AbstractTraditional Chinese medicine (TCM) has played a positive role in the management of hepatocarcinoma. Hepatocarcinoma patients may present Qi-stagnation, damp-heat, blood stasis, Qi-deficiency, Yin-deficiency REVIEWSubmit a

show abstract

“…In the presence of 8j and to some extent 8e , f-actin formed sporadic patches in the cytoplasm, which further supported the role of Grp94 inhibitors to modulate cell protrusion via f-actin reorganization (Figure 5B). 40 Immunofluorescence analysis showed that integrin α 2 is localized to the cell surface in untreated cells; however, in the presence of Grp94 inhibitors ( 8e and 8j ), integrin α 2 was localized as patches in the cytoplasm, supporting the role of Grp94 to traffic integrins to the cell membrane (Figure 5B). As shown in Figure 6, Grp94 inhibitors, 8e and 8j , inhibited cell motility.…”

Section: Resultsmentioning

confidence: 76%

Transformation of the Non-Selective Aminocyclohexanol-Based Hsp90 Inhibitor into a Grp94-Seletive Scaffold

et al. 2016

View full text Add to dashboard Cite

Glucose regulated protein 94 kDa, Grp94, is the endoplasmic reticulum (ER) localized isoform of heat shock protein 90 (Hsp90) that is responsible for the trafficking and maturation of toll-like receptors, immunoglobulins, and integrins. As a result, Grp94 has emerged as a therapeutic target to disrupt cellular communication, adhesion, and tumor proliferation, potentially with fewer side effects compared to pan-inhibitors of all Hsp90 isoforms. Although, the N-terminal ATP binding site is highly conserved among all four Hsp90 isoforms, recent cocrystal structures of Grp94 have revealed subtle differences between Grp94 and other Hsp90 isoforms that has been exploited for the development of Grp94-selective inhibitors. In the current study, a structure-based approach has been applied to a Grp94 nonselective compound, SNX 2112, which led to the development of 8j (ACO1), a Grp94-selective inhibitor that manifests ~440 nM affinity and >200-fold selectivity against cytosolic Hsp90 isoforms.

show abstract

F-Actin Reorganization and Inactivation of Rho Signaling Pathway Involved in the Inhibitory Effect of Coptidis Rhizoma on Hepatoma Cell Migration

Abstract: These results indicate that CRAE may act as a Rho/ROCK signaling inhibitor to suppress MHCC97-L cell migration in vitro and suggested that total alkaloids in Coptidis Rhizoma may be a potential agent for suppressing liver cancer invasion.

Cited by 48 publications

References 38 publications

Up-Regulation of TIMP-1 by Genipin Inhibits MMP-2 Activities and Suppresses the Metastatic Potential of Human Hepatocellular Carcinoma

Up-Regulation of TIMP-1 by Genipin Inhibits MMP-2 Activities and Suppresses the Metastatic Potential of Human Hepatocellular Carcinoma

Traditional Chinese medicine for prevention and treatment of hepatocarcinoma: From bench to bedside

Transformation of the Non-Selective Aminocyclohexanol-Based Hsp90 Inhibitor into a Grp94-Seletive Scaffold

Contact Info

Product

Resources

About