Honokiol, a natural biphenyl, inhibits in vitro and in vivo growth of breast cancer through induction of apoptosis and cell cycle arrest

Wolf, Ido; O’Kelly, James; Wakimoto, Naoki; Nguyen, Anh H.; Amblard, Franck; Karlan, Beth Y.; Arbiser, Jack L.; Koeffler, H. Phillip

doi:10.3892/ijo.30.6.1529

Cited by 50 publications

(65 citation statements)

References 42 publications

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“…Honokiol has been found to induce apoptosis in the colon cancer cell lines RKO and to inhibit the growth of RKO cells in murine xenografts (54). We have shown that honokiol prevents the growth of MDA-MD-231 breast cancer cells in murine xenografts (59). Of interest, MDA-MD-231 cells demonstrate mutant p53 and mutant K-ras, which is preferentially observed in the triplenegative breast cancer phenotype (24,62).…”

Section: In Vivo and In Vitro Antitumor Activity Of Honokiolmentioning

confidence: 84%

Honokiol, a Multifunctional Antiangiogenic and Antitumor Agent

Fried

Arbiser

2009

Antioxidants & Redox Signaling

279

245

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Honokiol is a small-molecule polyphenol isolated from the genus Magnolia. It is accompanied by other related polyphenols, including magnolol, with which it shares certain biologic properties. Recently, honokiol has been found to have antiangiogenic, antiinflammatory, and antitumor properties in preclinical models, without appreciable toxicity. These findings have increased interest in bringing honokiol to the clinic as a novel chemotherapeutic agent. In addition, mechanistic studies have tried to find the mechanism(s) of action of honokiol, for two major reasons. First, knowledge of the mechanisms of action may assist development of novel synthetic analogues. Second, mechanistic actions of honokiol may lead to rational combinations with conventional chemotherapy or radiation for enhanced response to systemic cancers. In this review, we describe the findings that honokiol has two major mechanisms of action. First, it blocks signaling in tumors with defective p53 function and activated ras by directly blocking the activation of phospholipase D by activated ras. Second, honokiol induces cyclophilin D, thus potentiating the mitochondrial permeability transition pore, and causing death in cells with wild-type p53. Knowledge of the dual activities of honokiol can assist with the development of honokiol derivatives and the design of clinical trials that will maximize the potential benefit of honokiol in the patient setting. Antioxid. Redox Signal. 11, 1139-1148.

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Section: In Vivo and In Vitro Antitumor Activity Of Honokiolmentioning

confidence: 84%

Honokiol, a Multifunctional Antiangiogenic and Antitumor Agent

Fried

Arbiser

2009

Antioxidants & Redox Signaling

279

245

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“…In addition, honokiol has a more obvious apoptosis-inducing effect on B-CLL cells than on normal mononuclear leukocytes (40). In vivo, honokiol was highly effective against SVR angiosarcoma (41) and breast cancer in nude mice (42) and in a human A549 lung cancer xenograft model (43) with the increased induction of apoptosis.…”

Section: Targeting Apoptosis Pathways In Cancer With Magnolol and Honmentioning

confidence: 89%

Targeting apoptosis pathways in cancer with magnolol and honokiol, bioactive constituents of the bark of <i>Magnolia officinalis </i>

Tang

Du³

et al. 2011

DD&T

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Magnolol and honokiol, main active compounds from the bark of Magnolia officinalis, have been found to have various pharmacological actions, including anti-oxidative, anti-inflammatory, anti-tumor, and anti-microbial properties, without appreciable toxicity. Recently, the anti-tumor activity of magnolol and honokiol has been extensively investigated. Magnolol and honokiol were found to possess anti-tumor activity by targeting the apoptosis pathways, which have been considered as targets for cancer therapies. This review will focus on the mechanisms by which magnolol and honokiol act on apoptosis pathways in cancer that have been characterized thus far, including the death receptormediated pathway, mitochondria-mediated pathway, caspase-mediated common pathway, and regulation of apoptosis-related proteins. These breakthrough findings may have important implications for targeted cancer therapy and modern applications of traditional Chinese medicine.

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“…Several studies have shown that honokiol has anti-angiogenic, antiproliferative and anti-invasive activities in colon and prostate cancer cells as well as in lung, breast and ovarian cancer cells (Yang et al, 2002;Wang et al, 2004;Wolf et al, 2007;Hahm et al, 2008;Fried and Arbiser, 2009). Magnolol has also been shown to induce apoptosis and suppress the proliferation of cancer cells, and inhibit tumour metastasis in various cancer cells, including those of the colon and prostate (Lin et al, 2002;Lee et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

4‐O‐methylhonokiol, a PPARγ agonist, inhibits prostate tumour growth: p21‐mediated suppression of NF‐κB activity

Lee

Ban

et al. 2013

British J Pharmacology

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BACKGROUND AND PURPOSEThe effects of 4-O-methylhonokiol (MH), a constituent of Magnolia officinalis, were investigated on human prostate cancer cells and its mechanism of action elucidated. EXPERIMENTAL APPROACHThe anti-cancer effects of MH were examined in prostate cancer and normal cells. The effects were validated in vivo using a mouse xenograft model. KEY RESULTSMH increased the expression of PPARg in prostate PC-3 and LNCap cells. The pull-down assay and molecular docking study indicated that MH directly binds to PPARg. MH also increased transcriptional activity of PPARg but decreased NF-kB activity. MH inhibited the growth of human prostate cancer cells, an effect attenuated by the PPARg antagonist GW9662. MH induced apoptotic cell death and this was related to G0-G1 phase cell cycle arrest. MH increased the expression of the cell cycle regulator p21, and apoptotic proteins, whereas it decreased phosphorylation of Rb and anti-apoptotic proteins. Transfection of PC3 cells with p21 siRNA or a p21 mutant plasmid on the cyclin D1/ cycline-dependent kinase 4 binding site abolished the effects of MH on cell growth, cell viability and related protein expression. In the animal studies, MH inhibited tumour growth, NF-kB activity and expression of anti-apoptotic proteins, whereas it increased the transcriptional activity and expression of PPARg, and the expression of apoptotic proteins and p21 in tumour tissues. CONCLUSIONS AND IMPLICATIONMH inhibits growth of human prostate cancer cells through activation of PPARg, suppression of NF-kB and arrest of the cell cycle. Thus, MH might be a useful tool for treatment of prostate cancer. AbbreviationCDK, cycline-dependent kinase; CNBr, cyanogen bromide; DAPI, 4',6-diamidino-2-phenylindole; GSK-3 b, glycogen synthase kinase 3 b; IAP1, inhibitor of apoptosis 1; iNOS, inducible NOS; MH, 4-O-methylhonokiol

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Honokiol, a natural biphenyl, inhibits in vitro and in vivo growth of breast cancer through induction of apoptosis and cell cycle arrest

Cited by 50 publications

References 42 publications

Honokiol, a Multifunctional Antiangiogenic and Antitumor Agent

Honokiol, a Multifunctional Antiangiogenic and Antitumor Agent

Targeting apoptosis pathways in cancer with magnolol and honokiol, bioactive constituents of the bark of <i>Magnolia officinalis </i>

4‐O‐methylhonokiol, a PPARγ agonist, inhibits prostate tumour growth: p21‐mediated suppression of NF‐κB activity

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