ArticleOncotarget2016
Honokiol bis-dichloroacetate (Honokiol DCA) demonstrates activity in vemurafenib-resistant melanoma in vivo.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The trial behind it
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Antibacterial, Photoprotective, Anti-Inflammatory, and Selected Anticancer Properties of Honokiol Extracted from Plants of the GenusInternational journal of molecular sciences · 2025Review
- DRP1, fission and apoptosis.Cell death discovery · 2025Review
- Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Flavones provide resistance to DUX4-induced toxicity via an mTor-independent mechanism.Cell death & disease · 2023Article
- Targeting the Vulnerabilities of Oncogene Activation.Cancers · 2023Article
- The application prospects of honokiol in dermatology.Dermatologic therapy · 2022Review
- Dichloroacetyl Amides of 3,5-Bis(benzylidene)-4-piperidones Displaying Greater Toxicity to Neoplasms than to Non-Malignant Cells.Medicines (Basel, Switzerland) · 2022Article
- Indolium 1 Exerts Activity against Vemurafenib-Resistant Melanoma In Vivo.Antioxidants (Basel, Switzerland) · 2022Article
- Mitochondrial Metabolism in Melanoma.Cells · 2021Review
- Article
- Honokiol Bis-Dichloroacetate Is a Selective Allosteric Inhibitor of the Mitochondrial Chaperone TRAP1.Antioxidants & redox signaling · 2021Article
- Synergistic killing effect of paclitaxel and honokiol in non-small cell lung cancer cells through paraptosis induction.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- Impact of pharmacological agents on mitochondrial function: a growing opportunity?Biochemical Society transactions · 2019Review
- Neurokinin-1 receptor is an effective target for treating leukemia by inducing oxidative stress through mitochondrial calcium overload.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Palladium based nanoparticles for the treatment of advanced melanoma.Scientific reports · 2019Article
- Magnolol induces cell death through PI3K/Akt-mediated epigenetic modifications boosting treatment of BRAF- and NRAS-mutant melanoma.Cancer medicine · 2019Article
- Overcoming Resistance to Cetuximab with Honokiol, A Small-Molecule Polyphenol.Molecular cancer therapeutics · 2018Article
- Cryptolepine inhibits melanoma cell growth through coordinated changes in mitochondrial biogenesis, dynamics and metabolic tumor suppressor AMPKα1/2-LKB1.Scientific reports · 2017Article
- Cancer Chemoprevention by Phytochemicals: Nature's Healing Touch.Molecules (Basel, Switzerland) · 2017Review
- Dual Inhibition of PI3K/Akt and mTOR by the Dietary Antioxidant, Delphinidin, Ameliorates Psoriatic Features In Vitro and in an Imiquimod-Induced Psoriasis-Like Disease in Mice.Antioxidants & redox signaling · 2017Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
The majority of human melanomas bears BRAF mutations and thus is treated with inhibitors of BRAF, such as vemurafenib. While patients with BRAF mutations often demonstrate an initial dramatic response to vemurafenib, relapse is extremely common. Thus, novel agents are needed for the treatment of these aggressive melanomas. Honokiol is a small molecule compound derived from Magnolia grandiflora that has activity against solid tumors and hematopoietic neoplasms. In order to increase the lipophilicity of honokiol, we have synthesized honokiol DCA, the dichloroacetate ester of honokiol. In addition, we synthesized a novel fluorinated honokiol analog, bis-trifluoromethyl-bis-(4-hydroxy-3-allylphenyl) methane (hexafluoro). Both compounds exhibited activity against A375 melanoma in vivo, but honokiol DCA was more active. Gene arrays comparing treated with vehicle control tumors demonstrated induction of the respiratory enzyme succinate dehydrogenase B (SDHB) by treatment, suggesting that our honokiol analogs induce respiration in vivo. We then examined its effect against a pair of melanomas, LM36 and LM36R, in which LM36R differs from LM36 in that LM36R has acquired vemurafenib resistance. Honokiol DCA demonstrated in vivo activity against LM36R (vemurafenib resistant) but not against parental LM36. Honokiol DCA and hexafluoro inhibited the phosphorylation of DRP1, thus stimulating a phenotype suggestive of respiration through mitochondrial normalization. Honokiol DCA may act in vemurafenib resistant melanomas to increase both respiration and reactive oxygen generation, leading to activity against aggressive melanoma in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.