Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Discover Oncology
Published in: Discover Oncology 1/2023

Open Access 01-12-2023 | Melanoma | Research

7,8-Dihydroxyflavone induces mitochondrial apoptosis and down-regulates the expression of ganglioside GD3 in malignant melanoma cells

Authors: Won Seok Ju, Sang Young Seo, Seong-eun Mun, Kyongtae Kim, Jin Ok Yu, Jae-Sung Ryu, Ji-Su Kim, Young-Kug Choo

Published in: Discover Oncology | Issue 1/2023

Login to get access

Abstract

Malignant melanoma is a skin cancer with poor prognosis and high resistance to conventional treatment. 7,8-dihydroxyflavone (7,8-DHF) has shown anti-carcinogenic, anti-inflammatory, anti-oxidant, and pharmacological effects in several types of cancer. However, the relationship between ganglioside expression and the anti-cancer effects of 7,8-DHF in melanoma is not fully understood. In the present study, 7,8-DHF exhibits specific anti-proliferation, anti-migration, and G2/M phase cell-cycle arrest effects on both melanoma cancer cell lines, and induces mitochondrial dysfunction and apoptosis, making it a potent candidate for anti-melanoma treatment. Furthermore, we confirmed that 7,8-DHF significantly reduces the expression levels of ganglioside GD3 and its synthase, which are known to be closely involved in carcinogenesis. Taken together, our findings suggest that 7,8-DHF may be a potent anti-cancer drug candidate for the treatment of malignant melanoma.
Appendix
Available only for authorised users
Literature
1.
Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, et al. Cancer treatment and survivorship statistics, 2021. CA Cancer J Clin. 2021;62:220–41.CrossRef
2.
DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, et al. Cancer treatment and survivorship statisitics, 2014. CA Cancer J Clin. 2014;64:252–71.PubMedCrossRef
3.
Orgaz JL, Sanz-Moreno V. Emerging molecular targets in melanoma invasion and mestastasis. Pigment Cell Melanoma Res. 2012;26:39–57.PubMedCrossRef
4.
Rosner K, Ropke C, Pless V, Skovgaard GL. Late type apoptosis and apoptosis free lethal effect of quercetin in human melanoma. Biosci Biotechnol Biochem. 2006;70:2169–77.PubMedCrossRef
5.
Weber J, Thompson JA, Hamid O, Minor D, Amin A, Ron I, et al. A randomize, double-blind, placebo-controlled, phase II study comparing the tolerability and efficacy of ipilimumab administered with or without prophylactic budesonide in patients with unresectable stage III or IV melanoma. Clin Cancer Res. 2009;15:5591–8.PubMedCrossRef
6.
O’day SJ, Maio M, Chiarion-Sileni V, Gajewski TF, Pehamberger H, Bondarenko IN, et al. Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study. Ann Oncol. 2010;21:1712–7.PubMedCrossRef
7.
Wolchok JD, Neyns B, Linette G, Negrier S, Lutzky J, Thomas L, et al. Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study. Lancet Oncol. 2010;11:155–64.PubMedCrossRef
8.
Hurez V, Padron A, Svatek RS, Curiel TJ. Considerations for successful cancer immunotherapy in aged hosts. Exp Gerontol. 2018;107:27–36.PubMedCrossRef
9.
Colombo PS, Flamini G, Christodoulou MS, Rodondi G, Vitalini S, Passarella D, et al. Farinose alpine primula speries: phytochemical and morphological investigations. Phytochemistry. 2014;98:151–9.PubMedCrossRef
10.
Castello NA, Nguyen MH, Tran JD, Cheng D, Green KN, LaFerla FM. 7,8-dihydroxyflavone, a small molecule TrkB agonist, improves spatial memory and increases thin spine density in a mouse model of alcheimer disease-like neuronal loss. PLoS ONE. 2014;9: e91453.PubMedPubMedCentralCrossRef
11.
Jang SW, Liu X, Yepes M, Shepherd KR, Miller GW, Liu Y, et al. A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone. Proc Natl Acad Sci USA. 2010;107:2687–92.PubMedPubMedCentralCrossRef
12.
Wu CH, Hung TH, Chen CC, Ke CH, Lee CY, Wang PY, et al. Post-injury treatment with 7,8-dihydroxyflavone, a TrkB receptor agonist, protects against experimental traumatic brain injury via PI3K/Akt signaling. PLoS ONE. 2014;9: e113397.PubMedPubMedCentralCrossRef
13.
Lee RH, Shin JC, Kim KH, Choi YH, Chae JI, Shim JH. Apoptotic effects of 7,8-dihydroxyflavone in human oral squamous cancer cells through suppression of Sp1. Oncol Rep. 2015;33:631–8.PubMedCrossRef
14.
Chen J, Chua KW, Chua CC, Yu H, Pei A, Chua BH, et al. Antioxidant activity of 7,8-dihydroxyflavone provides neuroprotection against glutamate-induced toxicity. Neurosci Lett. 2011;499:181–5.PubMedCrossRef
15.
16.
Huang WY, Cai YZ, Zhang Y. Natural phenolic compounds from medical herb and dietary plants: potential use for cancer prevention. Nutr Cancer. 2009;62:1–20.CrossRef
17.
Zhao J, Li P, Zhu H, Ge F, Liu J, Xia J, et al. 7,8-Dihydroxyflavone suppresses proliferation and induces apoptosis of human osteosarcoma cells. Acta Biochim Biophy Sin. 2021;53:903–11.CrossRef
18.
Chen Y, Chen H, Zhang W, Ding Y, Zhao T, Zhang M, et al. Bioaccessibility and biotransformation of anthocyanin monomers following in vitro simulated gastric-intestinal digestion and in vivo metabolism in rat. Food Funct. 2019;10:6052–61.PubMedCrossRef
19.
Sim DY, Sohng JK, Jung HJ. Anticancer activity of 7,8-dihydroxyflavone in melanoma cells via downregulation of α-MSH/cAMP/MITF pathway. Oncol Rep. 2016;36:528–34.PubMedCrossRef
20.
Park HY, Kim GY, Hyun JW, Kim ND, Kim CG, Kim WJ, et al. 7,8-dihydroxyflavone induces G1 arrest of the cell cycle in U937 human monocytic leukemia cells via induction of the Cdk inhibitor p27 and downregulation of pRB phosphorylation. Oncol Rep. 2012;28:353–7.PubMed
21.
Park HY, Kim GY, Kwon TK, Hwang HJ, Kim ND, Yoo YH, et al. Apoptosis induction of human leukemia U937 cells by 7,8-dihydroxyflavone hydrate through modulation of the Bcl-2 family of proteins and the MAPKs signaling pathway. Mutat Res. 2013;751:101–8.PubMedCrossRef
22.
Groux-Degroote S, Rodriguez-Walker M, Dewald JH, Daniotti JL, Delannoy P. Gangliosides in cancer cell signaling. Prog Mol Biol Transl Sci. 2018;156:197–227.PubMedCrossRef
23.
Allende ML, Proia RL. Lubricating cell signaling pathways with gangliosides. Curr Opin Struct Biol. 2002;12:587–92.PubMedCrossRef
24.
Li Y, Huang X, Wang C, Li Y, Luan M, Ma K. Ganglioside GM3 exerts opposite effects on motility via epidermal growth factor receptor and hepatocyte growth factor receptor-mediated migration signaling. Mol Med Rep. 2015;11:2959–66.PubMedCrossRef
25.
26.
Mansoori M, Mirzaei A, Abdi Rad I, Mahmodlou R, Mansouri F, SaeednejadZanjani L, et al. Upregulation of ganglioside GD2 synthase (GD2S), as a new putative cancer stem cell marker in breast carcinomas. Med J Islam Repub Iran. 2021;35:148.PubMedPubMedCentral
27.
Ju WS, Park SR, Seo SY, Cho JH, Min SH, Kim DH, et al. Relationship between ganglioside expression and anti-cancer effects of a plant-derived antibody in breast cancer cells. J Plant Biotechnol. 2019;46:217–27.CrossRef
28.
Shibuya H, Hamamura K, Hotta H, Matsumoto Y, Nishida Y, Hattori H, et al. Enhancement of malignant properties of human osteosarcoma cells with disialyl gangliosides GD2/GD3. Cancer Sci. 2012;103:1656–64.PubMedPubMedCentralCrossRef
29.
Chang HR, Cordon-Cardo C, Houghton AN, Cheung NK, Brennan MF. Expression of disialogangliosides GD2 and GD3 on human soft tissue sarcomas. Cancer. 1992;70:633–8.PubMedCrossRef
30.
Hakomori S. Carbohydrate-to-carbohydrate interaction, through glycosynapse, as a basis of cell recognition and membrane organization. Glycoconj J. 2004;21:125–37.PubMedCrossRef
31.
32.
Paris R, Morales A, Coll O, Sanchez-Reyes A, Garcia-Ruiz C, Fernandex-Checa JC. Ganglioside GD3 sensitizes human hepatoma cells to cancer theraphy. J Biol Chem. 2002;277:49870–6.PubMedCrossRef
33.
Zhang Q, Pan J, North PE, Yang S, Lubet RA, Wang Y, et al. Aerosolized 3-bromopyruvate inhibit lung tumorigenesis without causing liver toxicity. Cancer Prev Res. 2012;5:717–25.CrossRef
34.
Kwak DH, Seo YN, Lee JH, Park SJ, Cho YH, Kim JS, et al. GM1 induced the inflammatory response related to the Raf-1/MEK1/2/ERK1/2 pathway in co-culture of pig mesenchymal stem cells with RAW2647. Anim Cells Syst. 2018;22:157–64.CrossRef
35.
De Maria R, Lenti L, Malisan F, d’Agostino F, Tomassini B, Zeuner A, et al. Requirement for GD3 ganglioside in CD95- and ceramide-induced apoptosis. Science. 1997;277:1652–5.PubMedCrossRef
36.
Chi HJ, Chung DY, Choi SY, Kim JH, Kim GY, Lee JS, et al. Integrity of human sperm DNA assessed by the neutral comet assay and its relationship to semen parameters and clincal outcomes for the IVF-ET program. Clin Exp Reprod Med. 2011;38:10–7.PubMedPubMedCentralCrossRef
37.
Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. J Nutr Sci. 2016;5:1–15.CrossRef
38.
39.
Burrell RA, McGranahan N, Bartek J, Swanton C. The causes and consequences of genetic heterogeneity in cancer evolution. Nature. 2013;501:338–45.PubMedCrossRef
40.
41.
Marusyk A, Almendro V, Polyak K. Intra-tumour heterogeneity: a looking glass for cancer? Nat Rev Cancer. 2012;12:323–34.PubMedCrossRef
42.
Shackleton M, Quintana E, Fearon ER, Morrison SJ. Heterogeneity in cancer: cancer stem cells versus clonal evolution. Cell. 2009;138:822–9.PubMedCrossRef
43.
Junttila MR, Sauvage FJ. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature. 2013;501:346–54.PubMedCrossRef
44.
Straussman R, Morikawa T, Shee K, Barzily-Rokni M, Qian ZR, Du J, et al. Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature. 2012;487:500–4.PubMedPubMedCentralCrossRef
45.
Pan Z, Qu C, Chen Y, Chen X, Liu X, Hao W, et al. Bufotalin induces cell cycle arrest and cell apoptosis in human malignant melanoma A375 cells. Oncol Rep. 2019;41:2409–17.PubMed
46.
Sperka T, Wang J, Rudolph KL. DNA damage checkpoints in stem cells, ageing and cancer. Nat Rev Mol Cell Biol. 2012;13:579–90.PubMedCrossRef
47.
48.
Gu YR, Kim J, Na JC, Han WK. Mitochondrial metabolic reprogramming by SIRT3 regulation ameliorates drug resistance in renal cell carcinoma. PLoS ONE. 2022;17: e0269432.PubMedPubMedCentralCrossRef
49.
Cho JH, Jeon YJ, Park SM, Sin JC, Lee TH, Jung S, et al. Multifunctional effects of honokiol as anti-inflammatory and anti-cancer drug in human oral squamous cancer cells and xenograft. Biomaterials. 2015;53:274–84.PubMedCrossRef
50.
Polacheck WJ, Zervantonakis IK, Kamm RD. Tumor cell migration in complex microenviroments. Cell Mol Life Sci. 2013;70:1335–56.PubMedCrossRef
51.
Rippo MR, Malisan F, Ravagnan L, Tomassini B, Condo I, Costantini P, et al. GD3 ganglioside directly targets mitochondria in a bcl-2-controlled fashion. FASEB J. 2000;14:2047–54.PubMedCrossRef
52.
Kohla G, Stockfleth E, Schauer R. Gangliosides with 0-acetylated sialic acids in tumors of neuroectodermal origin. Neurochem Res. 2002;27:583–92.PubMedCrossRef
53.
Huang X, Li Y, He X, Chen Y, Wei W, Yang X, et al. Gangliosides and CD82 inhibit the motility of colon cancer by downregulating the phosphorylation of EGFR at different tyrosine sites and signaling pathway. Mol Med Rep. 2020;22:3994–4002.PubMed
54.
55.
Iwasawa T, Zhang P, Ohkawa Y, Momota H, Wakabayashi T, Ohmi Y, et al. Enhancement of malignant properties of human glioma cells by ganglioside GD3/GD2. Int J Oncol. 2018;52:1255–66.PubMed
56.
Garcia-Ruiz C, Colell A, Paris R, Fernandez-Checa JC. Direct interaction of GD3 ganglioside with mitochondria generates reactive oxygen species followed by mitochondrial permeability transition, cytochrome c release, and caspase activation. FASEB J. 2000;14:847–58.PubMedCrossRef
Metadata
Title
7,8-Dihydroxyflavone induces mitochondrial apoptosis and down-regulates the expression of ganglioside GD3 in malignant melanoma cells
Authors
Won Seok Ju
Sang Young Seo
Seong-eun Mun
Kyongtae Kim
Jin Ok Yu
Jae-Sung Ryu
Ji-Su Kim
Young-Kug Choo
Publication date
01-12-2023
Publisher
Springer US
Keywords
Melanoma
Melanoma
Published in
Discover Oncology / Issue 1/2023
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI
https://doi.org/10.1007/s12672-023-00643-0

Other articles of this Issue 1/2023

Discover Oncology 1/2023 Go to the issue

Correction

Correction: 7,8-Dihydroxyflavone induces mitochondrial apoptosis and down-regulates the expression of ganglioside GD3 in malignant melanoma cells

Research

The activity of cuproptosis pathway calculated by AUCell algorithm was employed to construct cuproptosis landscape in lung adenocarcinoma

Brief Communication

Association between vascular ultrasound features and DNA sequencing in breast cancer: a preliminary study

Research

MUC1 promotes lung metastases of liver cancer by impairing anti-tumor immunity

Review

Regulation of T cells by myeloid-derived suppressor cells: emerging immunosuppressor in lung cancer

Research

Veillonella parvula promotes the proliferation of lung adenocarcinoma through the nucleotide oligomerization domain 2/cellular communication network factor 4/nuclear factor kappa B pathway
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits