Targeting the intrinsic inflammatory pathway: honokiol exerts proapoptotic effects through STAT3 inhibition in transformed Barrett's cells

Yu, Chunhua; Zhang, Qiuyang; Zhang, Hui Ying; Zhang, Xi; Huo, Xiaofang; Cheng, Edaire; Wang, David H.; Arbiser, Jack L.; Spechler, Stuart J.; Souza, Rhonda F.

doi:10.1152/ajpgi.00033.2012

Cited by 27 publications

(19 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although EGCG (Nam et al , 2001) and HNK (Yu et al , 2012) may have other biological properties, studies showing that the AB 5 subtilase toxin, which cleaves GRP78 specifically, synergistically enhances the activity of ER stress inducers on melanoma cells (Martin et al , 2010) support the idea that chemical inhibitors of GRP78 may be effective as chemotherapeutic drugs. Nevertheless, although EGCG induces cell death and can overcome resistance to chemotherapeutic drugs (Ermakova et al , 2006; Virrey et al , 2008), on the basis of the present studies it did not have useful properties in combination with agents that induce ER stress.…”

Section: Discussionmentioning

confidence: 99%

Inducing apoptosis of cancer cells using small-molecule plant compounds that bind to GRP78

et al. 2013

View full text Add to dashboard Cite

Background:Glucose regulated protein 78 (GRP78) functions as a sensor of endoplasmic reticulum (ER) stress. The aim of this study was to test the hypothesis that molecules that bind to GRP78 induce the unfolded protein response (UPR) and enhance cell death in combination with ER stress inducers.Methods:Differential scanning calorimetry (DSC), measurement of cell death by flow cytometry and the induction of ER stress markers using western blotting.Results:Epigallocatechin gallate (EGCG), a flavonoid component of Green Tea Camellia sinensis, and honokiol (HNK), a Magnolia grandiflora derivative, bind to unfolded conformations of the GRP78 ATPase domain. Epigallocatechin gallate and HNK induced death in six neuroectodermal tumour cell lines tested. Levels of death to HNK were twice that for EGCG; half-maximal effective doses were similar but EGCG sensitivity varied more widely between cell types. Honokiol induced ER stress and UPR as predicted from its ability to interact with GRP78, but EGCG was less effective. With respect to cell death, HNK had synergistic effects on melanoma and glioblastoma cells with the ER stress inducers fenretinide or bortezomib, but only additive (fenretinide) or inhibitory (bortezomib) effects on neuroblastoma cells.Conclusion:Honokiol induces apoptosis due to ER stress from an interaction with GRP78. The data are consistent with DSC results that suggest that HNK binds to GRP78 more effectively than EGCG. Therefore, HNK may warrant development as an antitumour drug.

show abstract

Section: Discussionmentioning

confidence: 99%

Inducing apoptosis of cancer cells using small-molecule plant compounds that bind to GRP78

et al. 2013

View full text Add to dashboard Cite

show abstract

“…It has been shown to increase necrosis and apoptosis in transformed but not in nontransformed Barrett's cells and exhibit a similar effect on adenocarcinoma cells [134]. There is a great deal of preliminary work required on the effect of STAT3 inhibition in BE and EAC; however, it remains a potential future therapeutic target.…”

Section: Dietary Chemopreventionmentioning

confidence: 99%

The role of inflammation in cancer of the esophagus

O’Sullivan

Phelan

O’Hanlon

et al. 2014

Expert Review of Gastroenterology & Hepatology

View full text Add to dashboard Cite

Esophageal adenocarcinoma is the eighth most common malignancy worldwide. The overall prognosis is poor, with 5-year survival ranges of approximately 15-25%, and 30-50% for patients who can be treated with curative intent. There has been a marked increase in incidence of esophageal adenocarcinoma over the last 30 years, with chronic and severe reflux, diet and obesity identified as principal factors fuelling this rise in the West. Esophageal adenocarcinoma is an exemplar model of an inflammation-associated cancer. The key molecular pathways driving tumor development and influencing tumor biology are the subject of considerable research efforts, and is the principal focus of this review. In addition, the diverse range of changes occurring in the local immune response, tissue microenvironment, metabolic profile, intracellular signaling mechanisms and microRNA signatures are discussed, as well as novel targeted therapies.

show abstract

“…Honokiol may be used as an important therapeutic molecule to inhibit tumor angiogenesis and promote apoptosis [21, 26, 35]. Our present study for the first time shows that honokiol can promote apoptosis of renal cancer cells through the regulation of HO-1.…”

Section: Discussionmentioning

confidence: 53%

“…Thus, using inhibitors of these pathways in combination with CsA can be an ideal approach to attenuate the pro-tumorigenic effects of CsA without compromising its essential immunosuppressive functions. It has recently been suggested that honokiol, which has a great potential to inhibit tumor growth, may also down-regulate the Ras pathway [21, 26, 35]. A combination treatment with CsA and honokiol may be considered as a therapeutic strategy for preventing the development of post-transplantation renal cancer.…”

Section: Discussionmentioning

confidence: 99%

The natural product honokiol inhibits calcineurin inhibitor-induced and Ras-mediated tumor promoting pathways

et al. 2013

Self Cite

View full text Add to dashboard Cite

Although calcineurin inhibitors (CNIs) are very useful in preventing allograft rejection, they can mediate a rapid progression of post-transplantation malignancies. The CNI cyclosporine A (CsA) can promote renal tumor growth through activation of the proto-oncogene ras and over-expression of the angiogenic cytokine VEGF; the ras activation also induces over-expression of the cytoprotective enzyme HO-1, which promotes survival of renal cancer cells. Here, we show that the natural product honokiol significantly inhibited CsA-induced and Ras-mediated survival of renal cancer cells through the down-regulations of VEGF and HO-1. Thus, honokiol treatment may help to prevent tumor-promoting effects of CsA in transplant patients.

show abstract

Targeting the intrinsic inflammatory pathway: honokiol exerts proapoptotic effects through STAT3 inhibition in transformed Barrett's cells

Abstract: RF. Targeting the intrinsic inflammatory pathway: honokiol exerts proapoptotic effects through STAT3 inhibition in transformed Barrett's cells.

Cited by 27 publications

References 25 publications

Inducing apoptosis of cancer cells using small-molecule plant compounds that bind to GRP78

Inducing apoptosis of cancer cells using small-molecule plant compounds that bind to GRP78

The role of inflammation in cancer of the esophagus

The natural product honokiol inhibits calcineurin inhibitor-induced and Ras-mediated tumor promoting pathways

Contact Info

Product

Resources

About