In 2020, there were 2.3 million women diagnosed with breast cancer and 685 000 deaths globally. As of the end of 2020, there were 7.8 million women alive who were diagnosed with breast cancer in the past 5 years, making it the world’s most prevalent cancer. There are more lost disability-adjusted life years (DALYs) by women to breast cancer globally than any other type of cancer. Breast cancer occurs in every country of the world in women at any age after puberty but with increasing rates in later life. Approximately half of breast cancers develop in women who have no identifiable breast cancer risk factor other than gender (female) and age (over 40 years). Certain factors increase the risk of breast cancer including increasing age, obesity, harmful use of alcohol, family history of breast cancer, history of radiation exposure, reproductive history (such as age that menstrual periods began and age at first pregnancy), tobacco use and postmenopausal hormone therapy. – WHO 26. March 2021.
For over three decades, a mainstay and goal of clinical oncology has been the development of therapies promoting the effective elimination of cancer cells by apoptosis. This programmed cell death process is mediated by several signalling pathways (referred to as intrinsic and extrinsic) triggered by multiple factors, including cellular stress, DNA damage and immune surveillance. The interaction of apoptosis pathways with other signalling mechanisms can also affect cell death. – PMC8211386.
The mechanism of apoptosis is complex and involves many pathways. Defects can occur at any point along these pathways, leading to malignant transformation of the affected cells, tumour metastasis and resistance to anticancer drugs. Despite being the cause of problem, apoptosis plays an important role in the treatment of cancer as it is a popular target of many treatment strategies. The abundance of literature suggests that targeting apoptosis in cancer is feasible. – PMC3197541
Initiation and regulation of the two principal known apoptotic pathways. Epidemiological studies have described the beneficial effects of dietary polyphenols (flavonoids) on the reduction of the risk of chronic diseases, including cancer. Moreover, it has been shown that flavonoids, such as quercetin in apples, epigallocatechin-3-gallate in green tea and genistein in soya, induce apoptosis. This programmed cell death plays a critical role in physiological functions, but there is underlying dysregulation of apoptosis in numerous pathological situations such as Parkinson’s disease, Alzheimer’s disease and cancer. At the molecular level, flavonoids have been reported to modulate a number of key elements in cellular signal transduction pathways linked to the apoptotic process (caspases and bcl-2 genes) (PMID: 17321735)
Slovak Researchers examined the application of the possibilities of Flavin-7 (F7) within breast cancer animal models. During examination of breast cancer, NMU (N-Nitroso-N-methylurea is a highly reliable carcinogen, mutagen, and teratogen) in carcinogenicity-induced groups, (50mg/kg) followed by flavin7 at 0,3% and 3% concentrations were given to animals for 14 weeks. During the experiment, 75 (3 groupX25 animals) on average 33 days-old female rats of the Sprague-Dawley animals were being used. At the end of treatment, breast tumours were removed and prepared for histological and immunohistochemical analysis. In addition, using an in vitro cytotoxicity assay, apoptosis and proliferation after F7 treatment in human breast adenocarcinoma (MCF-7) cells were
performed.
The results of this experiment showed significant antitumour effects of fruit peel polyphenols (from F7) in rat mammary carcinogenesis. The results obtained suggested significant pro-apoptotic, anti-proliferative, and anti-angiogenic effects of F7 in rat mammary tumour cells in vivo and significant pro-apoptotic and anti-proliferative effects in human breast adenocarcinoma cells in vitro. Moreover, F7 demonstrated significant positive effect on plasma lipids in rats. Despite the optimistic results from preclinical research, epidemiologic studies have not provided sufficient evidence regarding cancer preventing activities of phytochemicals and/or plant-derived whole foods. Future studies, especially carefully designed and mechanismbased animal studies, may facilitate better understanding of the potential health benefits of dietary phytopharmaceuticals. Moreover, the dosing of phytopharmaceuticals in oncology patients will depend solely on the results from clinical research. Based on our results with F7, it can be concluded that daily consumption of fruits could be beneficial for the prevention of breast cancer and cardiovascular disease.
Apoptotic effect of F7 on MCF-7 cells.
a Apoptotic index of MCF-7 cells treated with 150 μg/ml of F7 for 24, 48, and 72 h. The results (mean ± SD) of three independent experiments are shown as the apoptotic index evaluated as a percentage of cells with fragmented nuclei from a total number of minimum 300 cells, *P < 0.05, **P < 0.01. b DNA fragmentation of MCF-7 cells after incubation with 150 μM μg/ml of F7 for 24, 48, and 72 h. C control (untreated cells)
Conclusion: „Our results reveal a substantial tumoursuppressive effect of F7 in the breast cancer model. We propose that the effects of phytochemicals present in this fruit extract are responsible for observed potent anti-cancer activities.”- Peter Kubatka (leader of the research).
Kubatka P, Kapinová A, Kello M, Kruzliak P, Kajo K, Výbohová D, Mahmood S, Murin R, Viera T, Mojžiš J, Zulli A, Péč M, Adamkov M, Kassayová M, Bojková B, Stollárová N, Dobrota D. Fruit peel polyphenols demonstrate substantial anti-tumour effects in the model of breast cancer. Eur J Nutr. 2016 Apr;55(3):955-65. doi: 10.1007/s00394-015-0910-5. Epub 2015 May 1. PMID: 25930965.
http://medpublics.com/docs/Fruit_peel_polyphenols.pdf
Acknowledgments This work was supported by the Scientific Grant Agency of the Ministry of Education of the Slovak Republic under the Contract No. VEGA 1/0071/13, VEGA 1/0043/12 and by the Slovak Research and Development Agency under the Contract No. APVV- 0325-07. This work was supported by the Grant “Martin Biomedical Centre” (ITMS: 26220220187), “Competence center for research and development in diagnosis and therapy”, code: 26220220153, and the Grant FNUSA-ICRC (No. CZ.1.05/1.1.00/02.0123), both projects cofunded from EU sources and European Regional Development Fund. This study was also supported by the project Medicínsky univerzitný park v Košiciach (MediPark, Košice) ITMS:26220220185 supported by Operational Programme Research and Development (OP VaV-2012/2.2/08-RO) (Contract No. OPVaV/12/2013). We thank to Eva
Jakubovicˇová for technical support.
