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Okayama University Medical Research Updates (OU-MRU) Vol.94

August 11, 2021

Source: Okayama University (JAPAN), Public Relations Division
For immediate release: 11 August 2021
Okayama University research: A berry vine found in Asia proves useful in combating lung cancer.

(Okayama, 11 August) In a study reported in Food and Chemical Toxicology, researchers from Okayama University describe the effects of Yamabudo, a garden vine, in mitigating lung cancer in the lab.

Lung cancer is known to be the most fatal form of cancer. Chemicals like 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) found in tobacco are usually the main culprits behind smoking-related lung cancer causing cancer biologists to actively explore targeted treatments. Now, a research group led by Associate Professor ARIMOTO-KOBAYASHI Sakae at Okayama University has reported the potential of a berry-producing vine, Vitis coignetiae Pulliat (colloquially known as Yamabudo in Japan), against lung cancer in mice.

The team has previously shown that juice extracted from the Yamabudo fruit and 2,6-dimethoxy-1,4-benzoquinone (DBQ), a chemical found within it, have protective effects against skin cancer. Thus, in this study the potential of both these chemicals was investigated. Mice were first treated with NNK to establish lung cancer models and tumors that subsequently developed within their lungs were assessed. After 30 weeks, mice given Yamabudo juice or DBQ showed greatly reduced tumor size. To understand the mechanism of Yamabudo further, human lung cancer cells were employed. NNK induces cancer by facilitating a chemical change in the DNA structure, known as DNA methylation. To mimic this process, cells were exposed to MNNG (a chemical that artificially induces DNA methylation) and the effects of Yamabudo were studied. Indeed, cells that were treated with Yamabudo juice or DBQ showed lower levels of DNA methylation.

The DNA methylation induced by NNK also plays a role in mutating the DNA, making all exposed cells susceptible to cancer. The methylated forms of DNA tend to form large complexes which can undergo damage more easily. Therefore, NNK-induced mutations were analyzed next to see if Yamabudo also plays a protective role in this regard. The number of NNK-induced mutations was, in fact, found to be considerably reduced by Yamabudo juice or DBQ. Yamabudo thus mitigated lung cancer by repairing the DNA damage caused by toxins. Lastly, the team also assessed biological pathways which typically help cancer cells proliferate. While all such pathways were active in the lung cancer cells, treatment with Yamabudo showed a dampening of these cancer-facilitating signals.

“Stimulation of repair of alkyl DNA adducts and suppressed growth signaling pathways are potential anti-tumorigenic targets of Yamabudo juice and DBQ in NNK-induced lung tumorigenesis,” conclude the researchers. Given the broad range of tumor-suppressing properties Yamabudo displays, it is one herbal medicine that should be explored further in lung cancer research.

Background
Yamabudo:
Vitis coignetiae Pulliat, also known as crimson glory vine or “Yamabudo” in Japan, is a berry-producing vine that grows primarily in East Asia. The juice extracted from Yamabudo berries comprises several chemical compounds that have medicinal properties. While its protective properties against skin cancer have briefly been shown before, this is the first study that explores the potential of Yamabudo in lung cancer.

DNA methylation: DNA methylation is a natural chemical process intended to regulate proper functioning of our genes. A chemical group known as the “methyl” group is usually bound onto specific regions of the DNA as a mechanism to prevent genes from being turned on when not in use. However, certain toxins and other external factors can also induce DNA methylation which sometimes prevents important genes (such as those that suppress cancer) from being active. Unfortunately, the methylated forms of DNA are passed on when cells replicate. DNA methylation thereby also abets the spread of cancer. Controlling DNA methylation is an important strategy in keeping certain cancers in check.

Reference
Sakae Arimoto-Kobayashi, Kensuke Sasaki, Ryoko Hida, Naoko Miyake, Nana Fujii, Yusuke Saiki, Kyohei Daimaru, Hirono Nakashima, Toshio Kubo, Katsuyuki Kiura. Chemopreventive effects and anti-tumorigenic mechanisms of 2,6-dimethoxy-1,4-benzoquinone, a constituent of Vitis coignetiae Pulliat (crimson glory vine, known as yamabudo in Japan), toward 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice. Food and Chemical Toxicology, Volume 154, August 2021, 112319.
DOI: https://doi.org/10.1016/j.fct.2021.112319
Chemopreventive effects and anti-tumorigenic mechanisms of 2,6-dimethoxy-1,4-benzoquinone, a constituent of Vitis coignetiae Pulliat (crimson glory vine, known as yamabudo in Japan), toward 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice

Correspondence to
Associate Professor ARIMOTO-KOBAYASHI Sakae, Ph.D.
Department of Cellular and Molecular Pharmaceutical Sciences,
Graduate School of Medicine, Dentistry and Pharmaceutical Science,
Okayama University, 1-1-1, Tsushima-naka, Kita-ku, Okayama
700-8530, Japan
E-mail: arimoto(a)okayama-u.ac.jp

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The whole volume : OU-MRU (1- )
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Vol.2:Ensuring a cool recovery from cardiac arrest
Vol.3:Organ regeneration research leaps forward
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Vol.5:Cell injections get to the heart of congenital defects
Vol.6:Fourth key molecule identified in bone development
Vol.7:Anticancer virus solution provides an alternative to surgery
Vol.8:Light-responsive dye stimulates sight in genetically blind patients
Vol.9:Diabetes drug helps towards immunity against cancer
Vol.10:Enzyme-inhibitors treat drug-resistant epilepsy
Vol.11:Compound-protein combination shows promise for arthritis treatment
Vol.12:Molecular features of the circadian clock system in fruit flies
Vol.13:Peptide directs artificial tissue growth
Vol.14:Simplified boron compound may treat brain tumours
Vol.15:Metamaterial absorbers for infrared inspection technologies
Vol.16:Epigenetics research traces how crickets restore lost limbs
Vol.17:Cell research shows pathway for suppressing hepatitis B virus
Vol.18:Therapeutic protein targets liver disease
Vol.19:Study links signalling protein to osteoarthritis
Vol.20:Lack of enzyme promotes fatty liver disease in thin patients
Vol.21:Combined gene transduction and light therapy targets gastric cancer
Vol.22:Medical supportive device for hemodialysis catheter puncture
Vol.23:Development of low cost oral inactivated vaccines for dysentery
Vol.24:Sticky molecules to tackle obesity and diabetes
Vol.25:Self-administered aroma foot massage may reduce symptoms of anxiety
Vol.26:Protein for preventing heart failure
Vol.27:Keeping cells in shape to fight sepsis
Vol.28:Viral-based therapy for bone cancer
Vol.29:Photoreactive compound allows protein synthesis control with light
Vol.30:Cancer stem cells’ role in tumor growth revealed
Vol.31:Prevention of RNA virus replication
Vol.32:Enzyme target for slowing bladder cancer invasion
Vol.33:Attacking tumors from the inside
Vol.34:Novel mouse model for studying pancreatic cancer
Vol.35:Potential cause of Lafora disease revealed
Vol.36:Overloading of protein localization triggers cellular defects
Vol.37:Protein dosage compensation mechanism unravelled
Vol.38:Bioengineered tooth restoration in a large mammal
Vol.39:Successful test of retinal prosthesis implanted in rats
Vol.40:Antibodies prolong seizure latency in epileptic mice
Vol.41:Inorganic biomaterials for soft-tissue adhesion
Vol.42:Potential drug for treating chronic pain with few side effects
Vol.43:Potential origin of cancer-associated cells revealed
Vol.44:Protection from plant extracts
Vol.45:Link between biological-clock disturbance and brain dysfunction uncovered
Vol.46:New method for suppressing lung cancer oncogene
Vol.47:Candidate genes for eye misalignment identified
Vol.48:Nanotechnology-based approach to cancer virotherapy
Vol.49:Cell membrane as material for bone formation
Vol.50:Iron removal as a potential cancer therapy
Vol.51:Potential of 3D nanoenvironments for experimental cancer
Vol.52:A protein found on the surface of cells plays an integral role in tumor growth and sustenance
Vol.53:Successful implantation and testing of retinal prosthesis in monkey eyes with retinal degeneration
Vol.54:Measuring ion concentration in solutions for clinical and environmental research
Vol.55:Diabetic kidney disease: new biomarkers improve the prediction of the renal prognosis
Vol.56:New device for assisting accurate hemodialysis catheter placement
Vol.57:Possible link between excess chewing muscle activity and dental disease
Vol.58:Insights into mechanisms governing the resistance to the anti-cancer medication cetuximab
Vol.59:Role of commensal flora in periodontal immune response investigated
Vol.60:Role of commensal microbiota in bone remodeling
Vol.61:Mechanical stress affects normal bone development
Vol.62:3D tissue model offers insights into treating pancreatic cancer
Vol.63:Promising biomarker for vascular disease relapse revealed
Vol.64:Inflammation in the brain enhances the side-effects of hypnotic medication
Vol.65:Game changer: How do bacteria play Tag ?
Vol.66:Is too much protein a bad thing?
Vol.67:Technology to rapidly detect cancer markers for cancer diagnosis
Vol.68:Improving the diagnosis of pancreatic cancer
Vol.69:Early gastric cancer endoscopic diagnosis system using artificial intelligence
Vol.70:Prosthetics for Retinal Stimulation
Vol.71:The nervous system can contribute to breast cancer progression
Vol.72:Synthetic compound provides fast screening for potential drugs
Vol.73:Primary intraocular lymphoma does not always spread to the central nervous system
Vol.74:Rising from the ashes—dead brain cells can be regenerated after traumatic injury
Vol.75:More than just daily supplements — herbal medicines can treat stomach disorders
Vol.76:The molecular pathogenesis of muscular dystrophy-associated cardiomyopathy
Vol.77:Green leafy vegetables contain a compound which can fight cancer cells
Vol.78:Disrupting blood supply to tumors as a new strategy to treat oral cancer
Vol.79:Novel blood-based markers to detect Alzheimer’s disease
Vol.80:A novel 3D cell culture model sheds light on the mechanisms driving fibrosis in pancreatic cancer
Vol.81:Innovative method for determining carcinogenicity of chemicals using iPS cells
Vol.82:Making memories — the workings of a neuron revealed
Vol.83:Skipping a beat — a novel method to study heart attacks
Vol.84:Friend to Foe—When Harmless Bacteria Turn Toxic
Vol.85:Promising imaging method for the early detection of dental caries
Vol.86:Plates and belts — a toolkit to prevent accidental falls during invasive vascular proceduresa
Vol.87:Therapeutic potential of stem cells for treating neurodegenerative disease
Vol.88:Nanotechnology for making cancer drugs more accessible to the brain
Vol.89:Studying Parkinson’s disease with face-recognition software
Vol.90:High levels of television exposure affect visual acuity in children
Vol.91:Meeting high demand: Increasing the efficiency of antiviral drug production in bacteria
Vol.92:Numerical modelling to assist the development of a retinal prosthesis
Vol.93:Repurposing cancer drugs: An innovative therapeutic strategy to fight bone cancer

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