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Effects of Fulvic Acid on Different Cancer Cell Lines

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Abstract

Humic substances are commonly found in decaying organic matter including plants, animal residues, sewage and soil. Although fulvic-acid accounts for ∼90% of all substances and its biological significance recognized for many years, there is still minimal scientific understanding the claims of its biological properties. However, these formulations contain numerous toxic elements that make their use clinically impossible. Recently, there has been development of a pure form of fulvic-acid, carbohydrate derived fulvic-acid (CHD-FA) that has been shown to be safe to use clinically and absent from environmental contaminants known to be harmful to the host. The aim of this study is to evaluate the effects of fulvic-acid on different cancer cells. Hep3B, HT29 and PC3 cells were treated different concentrations fulvic-acid for 48 and 72 h and cell proliferation was performed MTT test. Changes in the mRNA levels of apoptotic genes were also analyzed in PC3 cells. Fulvic-acid inhibited the proliferation of all the cell lines used in this study determined by MTT analysis. Specifically, Hep3B cells were found to be most sensitive for 48-hour application with 1.58–2.43 μg/μL IC50 value. Additionally, fulvic-acid significantly upregulated the apoptotic genes at mRNA levels compared to non-treated control group.
Proceedings 2017, 1, 1031; doi:10.3390/proceedings1101031 www.mdpi.com/journal/proceedings
Abstract
Effects of Fulvic Acid on Different Cancer Cell Lines
S.Kerem Aydin 1, Seher Dalgic 1, Merve Karaman 2, O.Faruk Kirlangic 3 and Hatice Yildirim 3,*
1 Sirri Yircali Anatolian High School, Balikesir 10020, Turkey
2 Department of Biology, Balikesir University, Balikesir 10145, Turkey
3 Department of Molecular Biology and Genetic, Balikesir University, Balikesir 10145, Turkey
* Correspondence: hbozkurt@balikesir.edu.tr or hatice_dna@hotmail.com; Tel.: +90-266-612-10-00-1122
Presented at the 2nd International Conference on Natural Products for Cancer Prevention and Therapy,
Kayseri, Turkey, 8–11 November 2017.
Publish: 14 November 2017
Abstract: Humic substances are commonly found in decaying organic matter including plants,
animal residues, sewage and soil. Although fulvic-acid accounts for 90% of all substances and its
biological significance recognized for many years, there is still minimal scientific understanding the
claims of its biological properties. However, these formulations contain numerous toxic elements
that make their use clinically impossible. Recently, there has been development of a pure form of
fulvic-acid, carbohydrate derived fulvic-acid (CHD-FA) that has been shown to be safe to use
clinically and absent from environmental contaminants known to be harmful to the host. The aim
of this study is to evaluate the effects of fulvic-acid on different cancer cells. Hep3B, HT29 and PC3
cells were treated different concentrations fulvic-acid for 48 and 72 h and cell proliferation was
performed MTT test. Changes in the mRNA levels of apoptotic genes were also analyzed in PC3
cells. Fulvic-acid inhibited the proliferation of all the cell lines used in this study determined by
MTT analysis. Specifically, Hep3B cells were found to be most sensitive for 48-hour application with
1.58–2.43 μg/μL IC50 value. Additionally, fulvic-acid significantly upregulated the apoptotic genes
at mRNA levels compared to non-treated control group.
Keywords: fulvic-acid; cancer; apoptosis
© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
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Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
... Study findings for fulvic acid properties conducted by Kishor et al. [7] , for example, suggest that humic substances, consisting of 60%-80% fulvic acids, have anti-cancerogenic properties. Their use may be beneficial in the treatment of cancer due to the chelating properties exhibited by heavy metals, as proven in several studies [8,9,10,11] . Until now, fulvic acids as a product have been used primarily to support plant growth and maintain adequate soil moisture. ...
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We carried out research to propose an innovative functional beverage targeted primarily at physically active people and based only on natural additives obtained from plants, waters, and soils. Fulvic acids have numerous health-enhancing qualities, which qualifies them to be valuable, organic drink additives. Not only is the content of minerals or vitamins of the product important to the consumer, but so are its organoleptic properties. Color and flavor, followed by price, are equally crucial elements in the design of a product in order to achieve market success. This paper presents the results of sensory analysis conducted on 16 drinks with various compositions. Functional water, along with fulvic acids, was also enriched with lemon, chokeberry, aloe, elderberry, and blackcurrant juice, etc. This analysis is the basic differentiator in determining the parameters of new food products. This study was carried out in collaboration with a trained expert panel, which guaranteed objectivity and ensured proper, reliable product quality assessment.
... A previous study showed that FA treatment at 1.58-2.43 μg/μL for 48 h or 72 h could inhibit cell proliferation and induce the gene expression of the apoptosis pathway in Hep3B, HT29, and PC3 cells [25]. Also, it has been argued that FA treatment at 5 μg/mL for 30 min can induce inflammatory response by activating nuclear factor-κB (NF-κB) pathway in RAW 264.7 cells [26]. ...
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Fulvic acid (FA), a humic substance, has several nutraceutical properties, including anti-inflammation, antimicrobial, and immune regulation abilities. However, systematic safety assessment remains insufficient. In the present study, a battery of toxicological studies was conducted per internationally accepted standards to investigate the genotoxicity and repeated-dose oral toxicity of FA. Sprague-Dawley (SD) rats or ICR mice were used. Compared to the control group, there were no significant changes (all p > 0.05) in all FA treatment groups in the bacterial reverse mutation test, in vitro mammalian chromosome aberration test, in vivo sperm shape abnormality assay, and in vivo mouse micronucleus assay. The acute toxicity test showed that no mortality or toxic effect was observed following oral administration of the maximum dose of 5,000 mg/kg BW/day to mice or rats. A 60-day subchronic study was conducted at 0 (control), 200, 1,000, and 5,000 mg/kg/day. Compared to the control group, there were no significant changes (all p > 0.05) in the body weights, feed consumption, clinical signs, hematology, clinical chemistry, organ weights, or histopathology examinations. In conclusion, the no-observed-adverse-effect-level (NOAEL) of FA supplementation from the 60-day study was determined to be 5,000 mg/kg body weight/day, the highest dose tested. Our findings suggest that the oral administration of FA may have higher safety.
... Kishor et al. [8] suggested that humic substances, consisting of 60-80% fulvic acids, have anticarcinogenic properties. They may be beneficial in cancer therapy due to their heavy metal chelating properties, binding of proteins delivering anticancer drugs, and inhibition of cancer cell proliferation [9][10][11]. Fulvic acids are also good free radical scavengers. ...
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The main purpose of the study was to investigate the quality of fulvic acid-based food products. The concentrations of Ca, K, Mg, Na, Cu, Fe, Mn, and Zn, and antioxidant capacities of fulvic acid concentrates and ready-to drink beverages available on the global market were determined. The concentrations of minerals were determined using microwave plasma-atomic emission spectrometry. Antioxidant capacity was expressed as total polyphenol (TP) and flavonoid (TF) contents, the trolox equivalent antioxidant capacity (TEAC) and ferric reducing ability of plasma (FRAP) values. The daily portion of eight out of 14 products realized 45–135% of recommended daily allowance (RDA) for Fe. One of ready-to-drink beverages was also a good source of Mg (about 40% of RDA), and another one of Mn (about 70% of RDA). The concentrations of TP and TF in ready-to-drink beverages varied from 6.5 to 187 µg/mL, whereas in concentrates, from 5886 to 19,844 µg/mL. Dietary supplements or food products with fulvic acids may be a good source of antioxidant polyphenolic compounds and some minerals.
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Demand for products made from the dry mass of Asian ginseng (Panax ginseng) is growing, but harvest is limited by fungal disease infection when ginseng is replanted in the same field. Rotated cropping with maize can cope with the replant limit, but it may take decades. We aimed to amend post-maize-cropping farmland soils for cultivating Asian ginseng, using effective microorganisms EMs and fulvic acid (FA) additives and detecting and comparing their effects on soil microbial diversity and physiochemical properties. Amendments promoted seedling survival and depressed disease-infection. Both EMs and FA increased the relative abundances of Pseudomonas, Flavobacterium, Duganella, and Massilia spp., but, decreased the relative abundances of Fusarium and Sistotrema. In addition, soil nutrient availability and properties that benefitted nutrient availabilities were promoted. In conclusion, amendments with EMs and FA improved the fertility of farmland soils, and the quality of Asian ginseng, and revealed the relationship between soil microbial diversity and physiochemical properties.
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