HHS public access

Author Manuscript
Nav Rev Cancer: Author manuscript ; available in PMC 2020 May 01.
Published in final edited form as: Nat Rev Cancer. 2019 May ; 19(5): 271–282. doi:10.1038/s41568-019-0135-7.

Targeting cancer vulnerabilities with high-dose vitamin C

Bryan Ngo, Justin M. Van Riper, Lewis C. Cantley, and Jihye Yun
Meyer Cancer Center, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

“Over the past decade, a growing number of studies have demonstrated that millimolar concentrations of pharmacological vitamin C can kill cancer cells in vitro and slow tumour growth in vivo.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526932/pdf/nihms-1025245.pdf
https://www.nature.com/articles/s41568-019-0135-7

HHS public access

Author Manuscript
Science. Author manuscript; available in PMC 2016 December 11.
Published in final edited form as: Science. 2015 December 11; 350(6266): 1391–1396. doi:10.1126/science.aaa5004.

Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH

Jihye Yun, Edouard Mullarky, Changyuan Lu, Kaitlyn N. Bosch, Adam Kavalier, Keith
Rivera, Jatin Roper, Iok In Christine Chio, Eugenia G. Giannopoulou, Carlo Rago,
Ashlesha Muley, John M. Asara, Jihye Paik, Olivier Elemento, Zhengming Chen,
Darryl J. Pappin, Lukas E. Dow, Nickolas Papadopoulos, Steven S. Gross, and Lewis C.
Cantley

“More than half of human colorectal cancers (CRCs) carry either KRAS or BRAF mutations, and
are often refractory to approved targeted therapies.”

“Vitamin C is selectively toxic to cells with mutant KRAS or BRAF alleles in colorectal cáncer cells.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4778961/pdf/nihms762868.pdf
https://science.sciencemag.org/content/350/6266/1391

ANTICANCER RESEARCH 28: 2727-2732 (2008)

HENRYK S. TAPER
Unité de Pharmacocinétique, Métabolisme, Nutrition et Toxicologie Université Catholique de Louvain, Bruxelles, Belgium

Altered Deoxyribonuclease Activity in Cancer Cells and its Role in Non Toxic Adjuvant Cancer Therapy with Mixed Vitamins C and K3

Joint administration of vitamin C and K3, which reactivated acid and alkaline DNase inhibited in cancer cells, caused tumor growth inhibition, a decrease of metastasis and potentiated or sensitized the chemotherapy both in vitro and in vivo.”

https://ar.iiarjournals.org/content/anticanres/28/5A/2727.full.pdf

https://pubmed.ncbi.nlm.nih.gov/19035302/

Journal of Translational Medicine

RESEARCH – Open Access.
Mikirova et al. Journal of Translational Medicine 2012, 10:189
http://www.translational-medicine.com/content/10/1/189

Effect of high-dose intravenous vitamin C on
inflammation in cancer patients

Nina Mikirova* , Joseph Casciari† , Andrea Rogers† and Paul Taylor

“The high dose intravenous ascorbic acid therapy affects C-reactive protein levels and pro-inflammation cytokines in cancer patients. In our study, we found that modulation of inflammation by IVC correlated with decreases in tumor marker levels. In summary, our data support the hypothesis that high dose intravenous ascorbate treatments may reduce inflammation in cancer patients.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480897/pdf/1479-5876-10-189.pdf

https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-10-189

Nature.com

Scientific reports
Open Access – Published: 28 March 2018

Vitamin C promotes apoptosis in breast cancer cells by increasing TRAIL expression

David W. Sant, Sushmita Mustafi, Christopher B. Gustafson, Joshua Chen, Joyce M. Slingerland & Gaofeng Wang 

“Treatment with vitamin C increases 5hmC content in breast cancer cells, changes the transcriptome, and induces apoptosis (cell death) by increasing expression of the apoptosis inducer gene, TNF-related apoptosis-inducing ligand (TRAIL).”

https://www.nature.com/articles/s41598-018-23714-7

Preclinical Studie

Scientific reports
Invest New Drugs (2011) 29:1314–1320
Received: 24 May 2010 /Accepted: 24 June 2010 / Published online: 13 July 2010
# The Author(s) 2010. This article is published with open access at Springerlink.com

Pankiller effect of prolonged exposure to menadione
on glioma cells: potentiation by vitamin C

Marina F. Vita & Nivedita Nagachar & Dimitrios Avramidis & Zahid M. Delwar & Mabel H. Cruz & Åke Siden & Kajsa M. Paulsson & Juan Sebastian Yakisich

“After short period of exposure data show that menadione alone or in combination with vitamin C provided similar concentration-response curves (and IC50 values). Prolonged exposure to these drugs was evaluated by their ability to kill 100% of glioma cells and prevent regrowth when cells are re-incubated in drug-free media. In this long-term assay, menadione: vitamin C at a ratio 1:100 showed higher anti-proliferative activity when compared to each drug alone and allowed to reduce each drug concentration between 2.5 to 5-fold. Similar antiproliferative effect was demonstrated in 8 patient derived glioblastoma cell cultures.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171656/pdf/10637_2010_Article_9489.pdf
https://pubmed.ncbi.nlm.nih.gov/20625795/

Impactjournals.com

www.impactjournals.com/oncotarget/
Oncotarget, Vol. 6, No. 31

Sub-apoptotic dosages of pro-oxidant vitamin cocktails sensitize human melanoma cells to NK cell lysis

Elisa Tremante1, Lory Santarelli2, Elisa Lo Monaco1, Camilla Sampaoli1, Tiziano Ingegnere1, Roberto Guerrieri3, Marco Tomasetti2,*, Patrizio Giacomini1,

“Alpha-tochopheryl succinate (αTOS), vitamin K3 (VK3) and vitamin C (ascorbic acid, AA) were previously shown to synergistically promote different death pathways in carcinoma cells, depending on their concentrations and combinations.”

“In the present study, we show that cell death/autoschizis may also be induced in melanoma cells at a standard low dosage

https://pubmed.ncbi.nlm.nih.gov/26427039/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741587/pdf/oncotarget-06-31039.pdf

Cancer Cell International

PRIMARY RESEARCH Open Access

Bonilla-Porras et al. Cancer Cell International 2011, 11:19
http://www.cancerci.com/content/11/1/19

Vitamin K3 and vitamin C alone or in
combination induced apoptosis in leukemia cells by a similar oxidative stress signalling mechanism

Elisa Tremante1, Lory Santarelli2, Elisa Lo Monaco1, Camilla Sampaoli1, Tiziano Ingegnere1, Roberto Guerrieri3, Marco Tomasetti2,*, Patrizio Giacomini1,

It is shown that vitamin K3- or vitamin C- induced apoptosis (cell death) in leukemia cells by oxidative stress mechanism involving superoxide anion radical and hydrogen peroxide generation, activation of NF-B, p53, c-Jun, protease caspase-3 activation and mitochondria depolarization leading to nuclei fragmentation. Cell death was more prominent when Jurkat and K562 cells are exposed to VC and VK3 in a ratio 1000:1 (10 mM: 10 μM) or 100:1 (300 μM: 3 μM), respectively.”

https://pubmed.ncbi.nlm.nih.gov/21663679/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3127817/pdf/1475-2867-11-19.pdf

Plos | One

Open Access Freely Available Online

Alpha-Tocopheryl Succinate Inhibits Autophagic Survival of Prostate Cancer Cells Induced by Vitamin K3 and Ascorbate to Trigger Cell Death

Marco Tomasetti1*, Linda Nocchi1, Jiri Neuzil2,3, Jacob Goodwin2, Maria Nguyen2, Lanfeng Dong2, Nicola Manzella1, Sara Staffolani1, Claudio Milanese4, Beatrice Garrone4, Renata Alleva5, Battista Borghi5, Lory Santarelli1, Roberto Guerrieri6

“A significant tumor growth inhibition was observed in the VK3 plus Ascorbic Acid treatment group; this effect was considerably enhanced at prolonged times of treatment when the two agents were combined with a-TOS.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525640/pdf/pone.0052263.pdf
https://pubmed.ncbi.nlm.nih.gov/23272231/

Journal of Experimental & Clinical Cancer Research

Review – Open Access
Kamarudin et al. Journal of Experimental & Clinical Cancer Research (2019) 38:491 https://doi.org/10.1186/s13046-019-1495-2

Metformin in colorectal cancer: molecular mechanism, preclinical and clinical aspects

Muhamad Noor Alfarizal Kamarudin1* , Md. Moklesur Rahman Sarker2,3* , Jin-Rong Zhou4 and Ishwar Parhar1

The current review depicts the beneficial use of metformin from preclinical, epidemiologic, and clinical studies as potential chemotherapeutic and adjuvant agent for CRC with notable association with T2DM”

“Furthermore, the ability of metformin to treat diabetes through AMPK modulation that also induces anticancer effect associated with the activation and/or inactivation of various downstream targets illustrate the double therapeutics value of metformin.”

https://pubmed.ncbi.nlm.nih.gov/31831021/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909457/pdf/13046_2019_Article_1495.pdf

HHS public access

Author Manuscript
Trends Pharmacol Sci. Author manuscript; available in PMC 2019 October 01.
Published in final edited form as: Trends Pharmacol Sci. 2018 October ; 39(10): 867–878. doi:10.1016/j.tips.2018.07.006.

Metformin as an Anticancer Agent

Ales Vancura1,*, Pengli Bu1, Madhura Bhagwat1, Joey Zeng1, and Ivana Vancurova1
1Department of Biological Sciences, St. John’s University, New York, NY 11439, USA

“Several clinical trials using metformin as a treatment in non-diabetic cancer patients have produced encouraging results.”

“The antitumor effects of metformin-activated AMPK are at least partially independent of the role of AMPK in regulation of gluconeogénesis.”

“Another study found a significantly decreased prostate specific antigen (PSA) after treatment of prostate cancer patients with metformin.”

https://pubmed.ncbi.nlm.nih.gov/30150001/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153060/pdf/nihms-1503308.pdf

Biomolecules | MDPI

Review

Metformin: The Answer to Cancer in a Flower?
Current Knowledge and Future Prospects of
Metformin as an Anti-Cancer Agent in Breast Cancer

Samson Mathews Samuel 1,* , Elizabeth Varghese 1, Peter Kubatka 2, Chris R. Triggle 3 and, Dietrich Büsselberg 1,*

 “Metformin has gained global attention for its potential as an anti-cancer drug and is currently being tested in in vitro cell-based assays, in vivo animal experiments, and in clinics at many cancer research facilities around the world.”

https://pubmed.ncbi.nlm.nih.gov/31835318/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995629/pdf/biomolecules-09-00846.pdf

eLive | Elivesciences.org

Research Article

Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis

William W Wheaton1†, Samuel E Weinberg1†, Robert B Hamanaka1, Saul Soberanes1, Lucas B Sullivan1, Elena Anso1, Andrea Glasauer1, Eric Dufour2, Gokhan M Mutlu1, GR Scott Budigner1, Navdeep S Chandel1*
Department of Medicine, The Feinberg School of Medicine, Northwestern – University, Chicago, United States; 2 – Institute of Biomedical Technology, University of Tampere, Tampere, Finland

Recent epidemiological and laboratory-based studies suggest that the anti-diabetic drug metformin prevents cancer progression.”

“Metformin inhibited celular proliferation in the presence of glucose, but induced cell death upon glucose deprivation, indicating that cancer cells rely exclusively on glycolysis for survival in the presence of metformin.”

https://pubmed.ncbi.nlm.nih.gov/24843020/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017650/pdf/elife02242.pdf

The review of DIABETIC STUDIES

Vol 10 No 4 2013

Metformin and Cancer

Natalia G. Vallianou1, Angelos Evangelopoulos2, and Christos Kazazis3
1 First Department of Internal Medicine, Evangelismos General Hospital, 10676 Athens, Greece.
2 Roche Diagnostics Hellas, 15125, Maroussi, Athens, Greece.
3 Honorary Lecturer, School of Medicine, University of Leicester, University Rd, Leicester, LE1 9HN, UK. Address correspondence to: Natalia G. Vallianou, MD, PhD, First Department of Internal Medicine, Evangelismos General Hospital, 45-49 Ipsilantou str, 10676 Athens, Greece, e-mail: natalia.vallianou@hotmail.com

Manuscript submitted October 10, 2013; resubmitted October 22, 2013; accepted October 30, 2013

“Metformin exerts in vitro inhibition of the proliferation of prostate, ovarian, and breast cáncer cells.”

“Metformin exerts its anti-tumor effects mainly through the AMPK/LKB1/TORC1 signaling pathway, thereby causing apoptosis in cancerous cells.”

https://pubmed.ncbi.nlm.nih.gov/24841876/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4160009/pdf/RevDiabeticStud-10-228.pdf

UROSURGERY (P SOORIAKUMARAN, SECTION EDITOR)

Curr Urol Rep (2017) 18: 46
DOI 10.1007/s11934-017-0693-8

Metformin and Prostate Cancer: a New Role for an Old Drug

Jessica Whitburn1 & Claire M. Edwards 1 & Prasanna Sooriakumaran1,2

“Metformin is an attractive anti-cancer agent in view of its well-documented safety record, well-characterised pharmacodynamics profile.”

“Early studies have shown benefits of metformin to inhibit cancer cell proliferation and improve metabolic syndrome in prostate cancer patients receiving androgen deprivation therapy (ADT).”

https://pubmed.ncbi.nlm.nih.gov/28444639/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405102/pdf/11934_2017_Article_693.pdf

Cancers | MDPI

Article

Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines

Margherita Luongo 1,†, Oliviero Marinelli 2,†, Laura Zeppa 2, Cristina Aguzzi 2, Maria Beatrice Morelli 2, Consuelo Amantini 3, Andrea Frassineti 1, Marianne di Costanzo 1, Alessandro Fanelli 4, Giorgio Santoni 2 and Massimo Nabissi 2,5,*

“Pancreatic cáncer hardly responds to chemotherapy or immunotherapy, and surgery is usually not an option in most patients”

“In cancer, O2/O3 was found to inhibit the growth of different human tumor cells (breast, colon, ovarian) without affecting non-tumor cell lines”

“cannabinoids can reduce cancer cell viability, proliferation, metastasis, and they induce cancer cell death in human glioblastoma multiforme, multiple myeloma, colorectal cancer, endometrial cancer, prostate carcinoma, and melanoma”

https://pubmed.ncbi.nlm.nih.gov/32992648/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600087/pdf/cancers-12-02774.pdf

Journal of Natural Science, Biology and Medicine

2011 Jan-Jun; 2(1): 66–70.

Ozone therapy: A clinical review

A. M. Elvis and J. S. Ekta

“Ozone administered at a concentration of between 30 and 55 μg/cc causes the greatest increase in the production of interferon and the greatest output of tumor necrosis factor and interleukin-2.”

“Ozone was also found to increase the host immunity by increasing the production of cytokine”

https://pubmed.ncbi.nlm.nih.gov/22470237/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312702/

Nutrients | MDPI

Review

Effects of Resveratrol against Lung Cancer: In Vitro and In Vivo Studies

Michael Yousef 1, Ioannis A. Vlachogiannis 2 and Evangelia Tsiani 1,2,* ID
1 Department of Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada; my11dq@brocku.ca
2 Centre for Bone and Muscle Health, Brock University, St. Catharines, ON L2S 3A1, Canada; yv17av@brocku.ca
* Correspondence: ltsiani@brocku.ca; Tel.: +1-905-688-5550 (ext. 3881)
Received: 17 October 2017; Accepted: 7 November 2017; Published: 10 November 2017

“Resveratrol (RSV) has been found to inhibit cancer cell proliferation, induce cell cycle arrest and apoptosis, and these anticancer effects may be due to its ability to modulate signaling molecules involved in these processes.”

“Resveratrol is capable of decreasing cancer cell proliferation and inhibiting tumor growth; inducing cell cycle arrest; inducing cell apoptosis; and inhibiting metastasis of lung cáncer.”

https://pubmed.ncbi.nlm.nih.gov/29125563/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707703/pdf/nutrients-09-01231.pdf

Biomolecules | MDPI

Review

The Plant-Derived Compound Resveratrol in Brain Cancer: A Review

Terezia Kiskova 1, Peter Kubatka 2, Dietrich Büsselberg 3 and Monika Kassayova 1,*
1 Department of Animal Physiology, Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Safarik – University, 04154 Kosice, Slovakia; terezia.kiskova@upjs.sk
2 Department of Medical Biology and Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius – University in Bratislava, 03601 Martin, Slovakia; peter.kubatka@uniba.sk
3 Department of Physiology and Biophysics, Weill Cornell Medicine in Qatar, Education City, Qatar Foundation, Doha 24144, Qatar; dib2015@qatar-med.cornell.edu
* Correspondence: monika.kassayova@upjs.sk
Received: 28 December 2019; Accepted: 16 January 2020; Published: 19 January 2020

“The significant antineoplastic potential of resveratrol was demonstrated in many cancer types when administered alone or in combination with diverse anticancer agents and targeted therapies.”

https://pubmed.ncbi.nlm.nih.gov/31963897/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023272/pdf/biomolecules-10-00161.pdf

Molecules | MDPI

Review

Resveratrol Inhibits the Migration and Metastasis of MDA-MB-231 Human Breast Cancer by Reversing TGF-β1-Induced Epithelial-Mesenchymal Transition

Yang Sun 1, Qian-Mei Zhou 1, Yi-Yu Lu 1, Hui Zhang 1, Qi-Long Chen 1, Ming Zhao 1,2 and Shi-Bing Su 1,*

“Our study found that resveratrol inhibits tumor growth and spontaneous lung metastasis of breast cancer without marked changes in liver or kidney function or body weight in a mouse MDA231 human breast cancer xenograft model.”

https://pubmed.ncbi.nlm.nih.gov/30901941/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471699/pdf/molecules-24-01131.pdf

Molecular Medicine REPORTS

20: 2783-2795, 2019

Resveratrol inhibits the invasion and metastasis of colon cancer through reversal of epithelial‑ mesenchymal transition via the AKT/GSK‑3β/Snail signaling pathway

LI YUAN1*, MENGMENG ZHOU2*, DAWEI HUANG3, HARPREET S. WASAN4, KAI ZHANG1, LEITAO SUN1, HONG HUANG5, SHENGLIN MA6, MINHE SHEN7 and SHANMING RUAN6,7

“Several studies have confirmed that resveratrol inhibits tumor invasion and metastasis.”

“Consistent with these findings, it was confirmed that resveratrol suppressed the migration and invasion of colon cáncer cells both in vitro and in vivo.”

https://pubmed.ncbi.nlm.nih.gov/31524255/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691253/pdf/mmr-20-03-2783.pdf

International Journal of Molecular Sciences | MDPI

Review

Resveratrol in Cancer Patients: From Bench to Bedside

Massimiliano Berretta 1,*,†, Alessia Bignucolo 2,†, Raffaele Di Francia 3, Francesco Comello 2, Gaetano Facchini 4, Manuela Ceccarelli 5, Rosario Vincenzo Iaffaioli 6, Vincenzo Quagliariello 7,‡ and Nicola Maurea 7,‡

“Resveratrol has been studied over the years as complementary and alternative medicine (CAM) for the therapy of cancer, metabolic and cardiovascular diseases like myocardial ischemia, myocarditis, cardiac hypertrophy and heart failure.”

“Resveratrol is able to modulate the expression of HIF-1α, thus reducing the fitness of Tumor microenvioronment to the expansion of the tumor.”

https://pubmed.ncbi.nlm.nih.gov/32331450/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216168/pdf/ijms-21-02945.pdf

Biotechnology Advances

Research review paper

Volume 36, Issue 6, 1 November 2018, Pages 1699-1708

The functional genomic studies of resveratrol in respect to its anti-cancer effects

Lukasz Huminiecki, Jarosław Horbańczuk

“Resveratrol’s anti-cancer effects can be studied either in vitro or in vivo. The effects fall into two classes: the well-documented anti-proliferative and pro-apoptotic effects on cancer cell lines; and slightly more hypothetical chemopreventive effects”

https://www.sciencedirect.com/science/article/pii/S0734975018300272?via%3Dihub
https://pubmed.ncbi.nlm.nih.gov/29476886/

JOURNAL OF MEDICINAL FOOD

J Med Food 16 (7) 2013, 602–617
# Mary Ann Liebert, Inc., and Korean Society of Food Science and Nutrition
DOI: 10.1089/jmf.2012.0222

Genes Related to Suppression of Malignant Phenotype Induced by Maitake D-Fraction in Breast Cancer Cells

Eliana Noelia Alonso, Manuela Orozco, Alvaro Eloy Nieto, and Gabriela Andrea Balogh
Biotechnology Laboratory, Science and Technology Center, Center of Renewable Natural Resources of the Semi-Arid Zone
(CERZOS), National Scientific and Technical Research Council (CONICET), Bahia Blanca, Buenos Aires, Argentina.

“According to the U.S. National Cancer Institute, polysaccharide complexes present in Maitake mushrooms appear to have significant anticáncer activity.”

“The present data shows that Maitake D-Fraction suppresses the breast tumoral phenotype through a putative molecular mechanism modifying the expression of certain genes that are involved in apoptosis stimulation, inhibition of cell growth and proliferation, cell cycle arrest, blocking migration and metastasis of tumoral cells, and inducing multidrug sensitivity.”

https://pubmed.ncbi.nlm.nih.gov/23875900/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3719462/pdf/jmf.2012.0222.pdf

Cancer Immunol Immunother

(2015) 64:237–247
DOI 10.1007/s00262-014-1628-6

ORIGINAL ARTICLE

Maitake mushroom extract in myelodysplastic syndromes (MDS): a phase II study

Kathleen M. Wesa · Susanna Cunningham-Rundles · Virginia M. Klimek ·
Emily Vertosick · Marci I. Coleton · K. Simon Yeung ·
Hong Lin · Stephen Nimer · Barrie R. Cassileth

“Maitake beta-glucan consumption improves neutrophil and monocyte function in lower-risk MDS patients.”

“In our breast cancer trial with oral Maitake beta-glucan, we assessed circulating levels of G-CSF in a subset of 6 patients comparing double baseline levels with 3 follow-up visits over a 12-week period. All patients showed positive or elevated G-CSF at baseline visits (11–80 pg/mL).”

https://pubmed.ncbi.nlm.nih.gov/25351719/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317517/pdf/262_2014_Article_1628.pdf

Oncotarget, 2018, Vol. 9, (No. 37), pp: 24837-24856

www.oncotarget.com
Review

B-glucans from Grifola frondosa and Ganoderma lucidum in breast cancer: an example of complementary and integrative medicine

Paola Rossi1, Raffaele Difrancia2, Vincenzo Quagliariello3, Elena Savino4, Paolo
Tralongo5, Cinzia Lucia Randazzo6 and Massimiliano Berretta7

“The antitumor effects of Maitake D-fraction have been attributed mainly to its immunostimulatory capabilities, as well as to direct antiproliferative and cytotoxic effects in human cancer cells, including prostate, bladder, liver, brain, blood (leukemia), and breast cells.”

“The most prominent functional changes were increased production of IL-2, IL-10, TNF-α, and IFN-γ by subsets of T cells.”

https://pubmed.ncbi.nlm.nih.gov/29872510/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5973856/pdf/oncotarget-09-24837.pdf

NIH Public Access

Author Manuscript

J Cancer Res Clin Oncol. Author manuscript; available in PMC 2013 August 23

A phase I/II trial of a polysaccharide extract from Grifola frondosa (Maitake mushroom) in breast cancer patients:
immunological effects

“Polysaccharide extracted from the fruit body of G. frondosa (Maitake extract) has demonstrated immunomodulatory effects in previous research. Maitake extract enhanced NK cell response, macrophage and cytotoxic T cell activity and antibody response, a study that also showed activation of alternative complement pathways.”

https://pubmed.ncbi.nlm.nih.gov/19253021/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751581/pdf/nihms479729.pdf

Journal of Evidence-Based Complementary & Alternative Medicine

2017, Vol. 22(4) 667-674
The Author(s) 2017
Reprints and permission: sagepub.com/journalsPermissions.nav
DOI: 10.1177/2156587217708524 journals.sagepub.com/home/cam

Induction Effect to Apoptosis by Maitake
Polysaccharide: Synergistic Effect of Its
Combination With Vitamin C in
Neuroglioma Cell

Lei Duan, PhD1,2,3, Xiao-Lu Wu, MM3, Fei Zhao, PhD1,2,4, Rong Zeng, PhD1,2,3, and Ke-Hu Yang, PhD1,2

“Polysaccharide extracted from the Maitake mushroom (MP) is considered as a potential anticancer agent. The present study was performed to investigate the cytotoxic effects of MP and vitamin C (VC) alone and in combination on the viability of humanneuroglioma M059 K cells in vitro. The inhibiting effect of combined treatment with MP and VC on M059 K cells indicates the mechanism of anticancer activity involved induction of cell apoptosis.”

“The combined use of MP and VC has significant antitumor effect.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871285/pdf/10.1177_2156587217708524.pdf
https://pubmed.ncbi.nlm.nih.gov/28528571/ 

International Journal of General Medicine

CASE REPORT

Possible disease remission in patient with invasive bladder cancer with D-fraction regimen

Srinivas Rajamahanty, Brandon Louie, Cormac O’Neill, Muhammad Choudhury, Sensuke Konno
Department of Urology, New York – Medical College, Valhalla, New York, USA

“We here report an 87-year-old White male patient with invasive bladder cancer who received an unconventional oral regimen of D-fraction, the bioactive extract of Maitake mushroom (Grifola frondosa). Despite a high risk for disease recurrence, follow-up yet indicated no clinical evidence of progression of residual disease or recurrence of invasive cancer.”

“The FDA also approved D-fraction for an Investigational New Drug (IND) application to conduct a Phase II pilot study on patients with advanced prostate and breast cancer, further granting its use in human cases.”

https://pubmed.ncbi.nlm.nih.gov/20360882/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2840560/pdf/ijgm-2-015.pdf

International Journal of General Medicine

Dovepress – Open access to scientific and medical research

REVIEW

Synergistic potentiation of D-fraction with vitamin C as possible alternative approach for cancer therapy

Sensuke Konno, Department of Urology, New York
Medical College, Valhalla, NY, USA

A number of in vitro and in vivo studies and limited clinical studies have demonstrated potent immunomodulatory and antitumor activities of Maitake D-fraction, implying its great potential in cancer treatment and prevention.”

https://pubmed.ncbi.nlm.nih.gov/20360893/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2840554/pdf/ijgm-2-091.pdf

Cancers | MDPI

REVIEW

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

Andrea M. Tomko 1,†, Erin G. Whynot 1,†, Lee D. Ellis 2 and Denis J. Dupré 1,*

“Cannabinoids display anticancer efects in several models by suppressing the proliferation, migration and/or invasion of cancer cells, as well as tumour angiogenesis.”

“Along with cannabinoids, cannabis contains several other compounds that have also been shown to exert anti-tumorigenic actions.”

https://pubmed.ncbi.nlm.nih.gov/32708138/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409346/pdf/cancers-12-01985.pdf

PORTLAND PRESS

Research Article
Bioscience Reports (2020) 40 BSR20201006
https://doi.org/10.1042/BSR20201006

β-glucan from Lentinus edodes inhibits breast cancer progression via the Nur77/HIF-1α axis

Xiuru Zhang1,*, Tingting Li1,*, Shuwen Liu1,*, Yiming Xu2, Minjun Meng2, Xiumin Li1, Zhichao Lin1, Qici Wu1,Yu Xue1, Yutian Pan1 and Gulimiran Alitongbieke1

“Lentinus Edodes (Shiitake Mushroom) inhibited the growth of breast tumors and the development of lung metastases from breast cáncer.”

“Lentinus Edodes (Shiitake Mushroom) inhibited the capability of breast tumor cells to invade to lung tissue.”

https://pubmed.ncbi.nlm.nih.gov/33245358/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736624/pdf/bsr-40-bsr20201006.pdf

Cancer Science

The official journal of the japanese cancer association | JCA

Oral ingestion of Lentinula edodes mycelia extract inhibits B16 melanoma growth via mitigation of regulatory T cell-mediated immunosuppression

Kousuke Tanaka 1, Satoru Ishikawa, Yasunori Matsui, Makoto Tamesada, Nanae Harashima, Mamoru Harada

“Our findings revealed that oral ingestion of Lentinula edodes (Shiitake Mushroom) extract restores melanoma-reactive T cells in animal models, and that this effect may be a result of mitigation of regulatory T cell-mediated immunosuppression.”

https://pubmed.ncbi.nlm.nih.gov/21261790/
https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1349-7006.2010.01841.x

International Journal of Molecular Sciences | MDPI

Article

LP1 from Lentinula edodes C91-3 Induces Autophagy, Apoptosis and Reduces Metastasis in Human Gastric Cancer Cell Line SGC-7901

Samana Batool 1, Thomson Patrick Joseph 1, Mushraf Hussain 2, Miza S. Vuai 1, Kavish. H. Khinsar 1, Syed Riaz Ud Din 1, Arshad Ahmed Padhiar 1, Mintao Zhong 1,Anhong Ning 1, Wei Zhang 1, Jing Cao 1 and Min Huang 1,*

“One of the most cultivated mushrooms is Lentinula edodes (Shiitake Mushroom), which is associated with a number of medicinal properties ranging from anti-microbial to anti-metastatic and anti-cancer to immunomodulation.”

“Our study demonstrated that LP1 from Lentinula edodes (Shiitake Mushroom) C91-3 had in vitro anticáncer potential against human gastric cancer cell line SGC-7901 and BGC 823.”

https://pubmed.ncbi.nlm.nih.gov/30274346/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213425/pdf/ijms-19-02986.pdf

Biological and Pharmaceutical Bulletin

2012;35(7):1014-21. doi: 10.1248/bpb.b110657.

Direct cytotoxicity of Lentinula edodes mycelia extract on human hepatocellular carcinoma cell line

Hiroshi Yukawa 1, Satoru Ishikawa, Takashi Kawanishi, Makoto Tamesada, Hironori Tomi

“Lentinula edodes mycelia (Shiitake Mushroom) has been reported to have anti-viral activity, hepatoprotective effects, immunomodulatory effects, and antitumor activity in vitro and in vivo.”

“In the present study, we found that Lentinufa Edodes etanol precipitate (L.E.P.) directly killed HepG2 (cáncer cell line) human Hepatocellular Carcinoma cells in a concentration- and timedependent manner, with less pronounced effects on normal hepatocytes under the same conditions in animal models.”

https://pubmed.ncbi.nlm.nih.gov/22791146/
https://www.jstage.jst.go.jp/article/bpb/35/7/35_b110657/_pdf/-char/en

Scientific Reports – Nature

Open Access | Published: 

Anti-tumor effect of β-glucan from Lentinus edodes and the underlying mechanism

Hui Xu, Siwei Zou, Xiaojuan Xu & Lina Zhang 

“This study focuses on the anti-tumor effect and the potential mechanism of a branched β-(1, 3)-glucan (LNT) extracted from Lentinus edodes.”

“The in vivo data indicated that Lentinus edodes extrac showed a profound inhibition ratio of ~75% against S-180 tumor growth, even significantly higher than the positive control of Cytoxan (~54%).”

“Besides, LNT inhibited angiogenesis by suppressing VEGF expression, leading to slow progression of tumors.”

https://pubmed.ncbi.nlm.nih.gov/27353254/
https://www.nature.com/articles/srep28802

Scientific Reports – Nature

Engineering dendritic cell vaccines to improve cancer immunotherapy

Caleb R. Perez & Michele De Palma

Dendritic cells (DCs) play key roles in tumor immunity and hold a hitherto unrealized potential for cancer immunotherapy.”

https://pubmed.ncbi.nlm.nih.gov/31776331/
https://www.nature.com/articles/s41467-019-13368-y