Honokiol produces anti‐neoplastic effects on melanoma cells in vitro

Mannal, Patrick; Schneider, John; Tangada, Abhilasha; McDonald, Debbie; McFadden, David W.

doi:10.1002/jso.21936

Cited by 26 publications

(15 citation statements)

References 11 publications

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“…203 Honokiol has been shown to inhibit proliferation in melanoma. 204,205 This has been suggested to occur through attenuation of AKT/mTOR and Notch signaling. 205 Further, honokiol has been shown to induce apoptosis through interaction with glucose-regulated protein 78, a sensor of endoplasmic reticulum stress.…”

Section: Phytochemicalsmentioning

confidence: 99%

Targeting drivers of melanoma with synthetic small molecules and phytochemicals

et al. 2015

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Melanoma is the least common form of skin cancer, but it is responsible for the majority of skin cancer deaths. Traditional therapeutics and immunomodulatory agents have not shown much efficacy against metastatic melanoma. Agents that target the RAS/RAF/MEK/ERK (MAPK) signaling pathway—the BRAF inhibitors vemurafenib and dabrafenib, and the MEK1/2 inhibitor trametinib—have increased survival in patients with metastatic melanoma. Further, the combination of dabrafenib and trametinib has been shown to be superior to single agent therapy for the treatment of metastatic melanoma. However, resistance to these agents develops rapidly. Studies of additional agents and combinations targeting the MAPK, PI3K/AKT/mTOR (PI3K), c-kit, and other signaling pathways are currently underway. Furthermore, studies of phytochemicals have yielded promising results against proliferation, survival, invasion, and metastasis by targeting signaling pathways with established roles in melanomagenesis. The relatively low toxicities of phytochemicals make their adjuvant use an attractive treatment option. The need for improved efficacy of current melanoma treatments calls for further investigation of each of these strategies. In this review, we will discuss synthetic small molecule inhibitors, combined therapies and current progress in the development of phytochemical therapies.

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Section: Phytochemicalsmentioning

confidence: 99%

Targeting drivers of melanoma with synthetic small molecules and phytochemicals

et al. 2015

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“…They observed the release of caspases-3, -8 and -9as well as poly (ADP-ribose) polymerase (PARP) cleavage and p53 activation upon honokiol treatment that led to DNA fragmentation and apoptosis. Cytotoxicity of honokiol was also associated with translocation of cytochrome c to cytosol in human melanoma cell lines (SK-MEL2 and MeWo) (40). Altogether, these studies indicate that honokiol is a promising candidate for the development of new strategies for the prevention of UV radiation-induced skin cancers in humans by targeting inflammatory mediators, cell cycle regulators, and cell survival signals in UVB-exposed skin.…”

Section: 0 Chemopreventive/ Chemotherapeutic Effects Of Honokiol Imentioning

confidence: 99%

Honokiol: A Novel Natural Agent for Cancer Prevention and Therapy

Arora

Singh

Piazza

et al. 2012

CMM

200

171

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Honokiol ((3’,5-di-(2-propenyl)-1,1’-biphenyl-2,2’-diol) is a bioactive natural product derived from Magnolia spp. Recent studies have demonstrated anti-inflammatory, anti-angiogenic, anti-oxidative and anti-cancer properties of honokiol in vitro and in preclinical models. Honokiol targets multiple signaling pathways including nuclear factor kappa B (NF-κB), signal transducers and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (m-TOR), which have great relevance during cancer initiation and progression. Furthermore, pharmacokinetic profile of honokiol has revealed a desirable spectrum of bioavailability after intravenous administration in animal models, thus making it a suitable agent for clinical trials. In this review, we discuss recent data describing the molecular targets of honokiol and its anti-cancer activities against various malignancies in pre-clinical models. Evaluation of honokiol in clinical trials will be the next step towards its possible human applications.

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“…Honokiol is a biphenolic bioactive compound isolated from the genus Magnolia Officinalis and shows multifunctional antitumor activities, such as cell cycle regulation, induction of apoptosis and inhibition of metastasis in several cancers [24, 25, 26]. Herein, this is the first study to investigate the novel efficacy of Honokiol targeting on GBM stem-like cells.…”

Section: Discussionmentioning

confidence: 99%

Elimination of Cancer Stem-Like Cells and Potentiation of Temozolomide Sensitivity by Honokiol in Glioblastoma Multiforme Cells

et al. 2015

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Glioblastoma multiforme (GBM) is the most common adult malignant glioma with poor prognosis due to the resistance to radiotherapy and chemotherapy, which might be critically involved in the repopulation of cancer stem cells (CSCs) after treatment. We had investigated the characteristics of cancer stem-like side population (SP) cells sorted from GBM cells, and studied the effect of Honokiol targeting on CSCs. GBM8401 SP cells possessed the stem cell markers, such as nestin, CD133 and Oct4, and the expressions of self-renewal related stemness genes, such as SMO, Notch3 and IHH (Indian Hedgehog). Honokiol inhibited the proliferation of both GBM8401 parental cells and SP cells in a dose-dependent manner, the IC50 were 5.3±0.72 and 11±1.1 μM, respectively. The proportions of SP in GBM8401 cells were diminished by Honokiol from 1.5±0.22% down to 0.3±0.02% and 0.2±0.01% at doses of 2.5 μM and 5 μM, respectively. The SP cells appeared to have higher expression of O 6-methylguanine-DNA methyltransferase (MGMT) and be more resistant to Temozolomide (TMZ). The resistance to TMZ could be only slightly reversed by MGMT inhibitor O 6-benzylguanine (O 6-BG), but markedly further enhanced by Honokiol addition. Such significant enhancement was accompanied with the higher induction of apoptosis, greater down-regulation of Notch3 as well as its downstream Hes1 expressions in SP cells. Our data indicate that Honokiol might have clinical benefits for the GBM patients who are refractory to TMZ treatment.

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Honokiol produces anti‐neoplastic effects on melanoma cells in vitro

Abstract: It appears that honokiol is an effective inhibitor of cultured human melanoma cells.

Cited by 26 publications

References 11 publications

Targeting drivers of melanoma with synthetic small molecules and phytochemicals

Targeting drivers of melanoma with synthetic small molecules and phytochemicals

Honokiol: A Novel Natural Agent for Cancer Prevention and Therapy

Elimination of Cancer Stem-Like Cells and Potentiation of Temozolomide Sensitivity by Honokiol in Glioblastoma Multiforme Cells

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