Targeting apoptosis pathways in cancer with magnolol and honokiol, bioactive constituents of the bark of &lt;i&gt;Magnolia officinalis &lt;/i&gt;

Xu, Huanli; Tang, Wei; Du, Guanhua; Kokudo, Norihiro

doi:10.5582/ddt.2011.v5.5.202

Cited by 45 publications

(27 citation statements)

References 85 publications

(96 reference statements)

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“…Numerous signaling pathways have been implicated in the regulation of apoptosis by magnolol [27]. Magnolol triggers the release of Bid, Bax and cytochrome c from mitochondria, and induces apoptosis via a caspase-independent pathway in non-small cell lung cancer cells [7].…”

Section: Discussionmentioning

confidence: 99%

2-O-Methylmagnolol Induces Apoptosis and Inhibits IL-6/STAT3 Signaling in Oral Squamous Cell Carcinoma

Wang

Fang

et al. 2018

Cell Physiol Biochem

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Background/Aims: 2-O-methylmagnolol (MM1), a derivative of magnolol bearing one methoxy moiety, has been shown to display improved anti-tumor activity against skin cancers. In this study, we examined the anti-tumor effects of magnolol and MM1 on oral squamous cell carcinoma (OSCC). Methods: Trypane blue staining and clonogenic assays were performed to determine the cytotoxic effects of magnolol and MM1 in OSCC cells. Migration and matrigel invasion assays were carried out to examine the metastasis effects of magnolol and MM1 in OSCC cells. IL6-stimulation, Western blot, and immunohistochemistry were used to investigate the IL-6/STAT3 signaling and apoptosis. A bioluminescent mouse model of orthotopically implanted SAS cells was used to determine the anti-tumor activity of MM1 in vivo. Results: MM1 displays greater activity than magnolol on affecting the cytotoxicity, migration, and invasion of OSCC cells cultured in vitro. The improved anti-tumor activity of MM1 was shown to associate with its greater activity to inhibit STAT3 signaling and to induce apoptosis in the OSCC. In addition, we presented evidence that MM1 is effective in inhibiting the growth of orthotopic implanted OSCC cells in vivo. Conclusion: Our data indicate that MM1 displays greater anti-tumor activity than magnolol in OSCC and is an attractive agent to be further explored for its potential clinical application.

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Section: Discussionmentioning

confidence: 99%

2-O-Methylmagnolol Induces Apoptosis and Inhibits IL-6/STAT3 Signaling in Oral Squamous Cell Carcinoma

Wang

Fang

et al. 2018

Cell Physiol Biochem

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“…Honokiol is an important bioactive compound present in Magnolia bark extracts, which has been used as a folk remedy for centuries in China, South Korea, and Japan to treat gastrointestinal disorders, cough, anxiety, stroke, and allergic diseases (4). Honokiol has been reported to have a variety of broad mechanisms of action, such as anti-inflammatory activity (5, 6), along with antiangiogenic (7) and cardio-beneficiating (8, 9), and neuro-protective activity (10, 11), without appreciable toxicity.…”

Section: Introductionmentioning

confidence: 99%

Honokiol Inhibits Lung Tumorigenesis through Inhibition of Mitochondrial Function

Pan

Zhang

Liu

et al. 2014

Cancer Prevention Research

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Honokiol is an important bioactive compound found in the bark of Magnolia tree. It is a non-adipogenic PPARγ agonist, and capable of inhibiting the growth of a variety of tumor types both in vitro and in xenograft models. However, to fully appreciate the potential chemopreventive activity of honokiol, a less artificial model system is required. To that end, this study examined the chemopreventive efficacy of honokiol in an initiation model of squamous cell lung cancer (SCC). This model system uses the carcinogen N-nitroso-trischloroethylurea (NTCU) which is applied topically, reliably triggering the development of SCC within 24–26 weeks. Administration of honokiol significantly reduced the percentage of bronchial that exhibit abnormal lung SCC histology from 24.4% bronchial in control to 11.0% bronchial in honokiol treated group (p= 0.01) while protecting normal bronchial histology (present in 20.5% of bronchial in control group and 38.5% of bronchial in honokiol treated group (p= 0.004)). P63 staining at the SCC site confirmed the lung SCCs phenotype. In vitro studies revealed that honokiol inhibited lung SCC cells proliferation, arrested cells at the G1/S cell cycle checkpoint, while also leading to increased apoptosis. Our study showed that interfering with mitochondrial respiration is a novel mechanism by which honokiol increased generation of reactive oxygen species (ROS) in the mitochondria, triggered apoptosis, and finally leads to the inhibition of lung SCC. This novel mechanism of targeting mitochondrial suggests honokiol as a potential lung SCC chemopreventive agent.

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“…Recent studies have shown that honokiol possesses wide-ranging biological and clinically relevant properties, without an appreciable degree of toxicity5. Several studies have reported that honokiol induces cell-cycle arrest and apoptosis in cancer cells67 and inhibits tumor-associated lymphangiogenesis and metastasis in lung carcinoma models induced by vascular endothelial growth factor8. Zhang et al 9.…”

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confidence: 99%

Honokiol as a specific collagen receptor glycoprotein VI antagonist on human platelets: Functional ex vivo and in vivo studies

Lee

Chang

et al. 2017

Sci Rep

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Honokiol, derived from Magnolia officinalis, has various pharmacological properties. Platelet activation plays a critical role in cardiovascular diseases. Honokiol has been reported to inhibit collagen-stimulated rabbit platelet aggregation. However, detailed further studies on the characteristics and functional activity of honokiol in platelet activation are relatively lacking. In the present study, honokiol specifically inhibited platelet aggregation and Ca+2 ion mobilization stimulated with collagen or convulxin, an agonist of glycoprotein (GP) VI, but not with aggretin, an agonist of integrin α2β1. Honokiol also attenuated the phosphorylation of Lyn, PLCγ2, PKC, MAPKs, and Akt after convulxin stimulation. Honokiol have no cytotoxicity in zebrafish embryos. Honokiol diminished the binding of anti-GP VI (FITC-JAQ1) mAb to human platelets, and it also reduced the coimmunoprecipitation of GP VI-bound Lyn after convulxin stimulation. The surface plasmon resonance results revealed that honokiol binds directly to GP VI, with a KD of 289 μM. Platelet function analysis revealed that honokiol substantially prolonged the closure time in human whole blood and increased the occlusion time of thrombotic platelet plug formation in mice. In conclusion, honokiol acts as a potent antagonist of collagen GP VI in human platelets, and it has therapeutic potential in the prevention of the pathological thrombosis.

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

Cited by 45 publications

References 85 publications

2-O-Methylmagnolol Induces Apoptosis and Inhibits IL-6/STAT3 Signaling in Oral Squamous Cell Carcinoma

2-O-Methylmagnolol Induces Apoptosis and Inhibits IL-6/STAT3 Signaling in Oral Squamous Cell Carcinoma

Honokiol Inhibits Lung Tumorigenesis through Inhibition of Mitochondrial Function

Honokiol as a specific collagen receptor glycoprotein VI antagonist on human platelets: Functional ex vivo and in vivo studies

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