Redox cycling of endogenous copper by ferulic acid leads to cellular DNA breakage and consequent cell death: A putative cancer chemotherapy mechanism

Sarwar, Tarique; Zafaryab,; Husain, Mohammed Amir; Ishqi, Hassan Mubarak; Rehman, Sufia; Rizvi, M. Moshahid Alam; Tabish, Mohammad

doi:10.1016/j.taap.2015.09.018

Cited by 32 publications

(26 citation statements)

References 54 publications

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“…So, DL data support the idea that cationic NLCs 64 were able to sensitize glioblastoma cells to the treatment, yielding significant improvements over the untreated cells. On the other hand, the reduced effect of FA treatment on U-87 MG cells observed on DL emission supports the idea that FA could not enter into mitochondria, but could be able to activate apoptosis and block cell cycle progression by directly acting on DNA 65 . In fact, free FA induced apoptosis pathway activation, as revealed by the increase of caspase-3 and PARP-1 cleavage, reducing also the expression levels of the nuclear transcription factor c-Myc.…”

Section: Discussionsupporting

confidence: 65%

Synergic pro-apoptotic effects of Ferulic Acid and nanostructured lipid carrier in glioblastoma cells assessed through molecular and Delayed Luminescence studies

Grasso

Dell’Albani

Carbone

et al. 2020

Sci Rep

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Herein, we assessed the effect of Ferulic Acid (FA), a natural antioxidant with anti-cancer effect, on the human glioblastoma cells through molecular and Delayed Luminescence (DL) studies. DL, a phenomenon of ultra-week emission of optical photons, was used to monitor mitochondrial assessment. The effect of FA loaded in nanostructured lipid carriers (NLCs) was also assessed. To validate NLCs as a drug delivery system for glioblastoma treatment, particular attention was focused on their effect. We found that free FA induced a significant decrease in c-Myc and Bcl-2 expression levels accompanied by the apoptotic pathway activation. Blank NLCs, even if they did not induce cytotoxicity and caspase-3 cleavage, decreased Bcl-2, ERK1/2, c-Myc expression levels activating PARP-1 cleavage. The changes in DL intensity and kinetics highlighted a possible effect of nanoparticle matrix on mitochondria, through the involvement of the NADH pool and ROS production that, in turn, activates ERK1/2 pathways. All the effects on protein expression levels and on the activation of apoptotic pathway appeared more evident when the cells were exposed to FA loaded in NLCs. We demonstrated that the observed effects are due to a synergic pro-apoptotic influence exerted by FA, whose bioavailability increases in the glioblastoma cells, and NLCs formulation.Glioblastoma multiforme (GBM), also known as grade IV astrocytoma, represents the most prevalent and aggressive brain cancer. It is characterized by glial cells and has finger-like tentacles that infiltrate the brain, which make them very difficult to remove with surgical procedures. GBM exhibits a high level of resistance to conventional chemotherapy and radiotherapy, also due to the existence of blood-brain barrier (BBB), glioma stem cells and complex network of multiple modified signalling pathways 1 . The most frequent aberrant expression is represented by the dysregulation of extracellular signal-regulated protein kinase (ERK), which is associated with poor survival of the patients. The ERK isoforms (p42/44 or ERK1/ERK2) by interacting with specific phosphorylation substrates, play a pivotal role in the control of several cellular processes involved in proliferation, as well as activation of transcription factors, apoptosis and the control of cellular process 2,3 . In addition, the transcription factor c-Myc has been recognized as an important regulator of stem cell biology implicated with GBM malignancy and stemness 4 , as it contributes to proliferation, growth and survival of GBM stem cells 5 . GBM has been also related to the impairment of mitochondrial metabolic capacity, which leads to the alteration in energy production 6,7 and is characterized by an overexpression of Bcl-2 8 . This protein can regulate transition pores permeability of the outer mitochondrial membrane and block pro-apoptotic proteins 9 . Furthermore, it has been identified a novel www.nature.com/scientificreports www.nature.com/scientificreports/ interaction between Bcl-2 and (ADP-ribose) polymerase (PARP) 10 , t...

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Section: Discussionsupporting

confidence: 65%

Synergic pro-apoptotic effects of Ferulic Acid and nanostructured lipid carrier in glioblastoma cells assessed through molecular and Delayed Luminescence studies

Grasso

Dell’Albani

Carbone

et al. 2020

Sci Rep

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“…FA may modulate the status of lipid per-oxidation and antioxidants to contribute to anti-proliferative activity during the 7,12-dimethylbenz[a] anthracene-induced skin carcinogenesis 8. FA shows cytotoxicity and apoptosis activity through prompting oxidative DNA breakage enhanced by endogenous copper to kill SiHa cervical cancer cells and HepG2 hepatocellular carcinoma cells without affecting normal cells 11. In this study, both SaOS-2 and MG63 cell viabilities were significantly decreased due to exposure to FA.…”

Section: Discussionmentioning

confidence: 56%

Ferulic acid promoting apoptosis in human osteosarcoma cell lines

Zhang¹,

Wu²,

Yang³

2017

Pak J Med Sci

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Objective:To explore the promoting apoptosis and antitumor activities of ferulic acid (FA) in human osteosarcoma and its potential mechanism.Methods:The SaOS-2 and MG63 osteosarcoma cell lines were opted to experiment and these cells were, respectively, cultured with various concentrations of FA (0 μM, 10 μM, 20 μM, 40 μM) for 72 hours at 37°C. The viabilities of the FA treated cells were monitored by MTT. Apoptosis cells were evaluated using annexin V/PI by flow cytometry. Apoptosis proteins caspase-3, procaspase-3, Bcl-2 and Bax were detected by western blot. Expressions of apoptotic genes Bcl-2 and Bax were quantified by qPCR.Results:The cell viabilities were critically declined in the concentration-dependent manner in FA groups (P < 0.01). The apoptosis cells were increased proportionately with the concentration of FA (P < 0.05). The procaspase-3 protein contents, and Bcl-2 mRNA and protein contents were significantly decreased while caspase-3 protein contents, and Bax mRNA and protein contents were concomitantly increased in the concentration-dependent manner in FA groups (P < 0.05). The response to FA by the SaOS-2 osteosarcoma cell was similar with the MG63 osteosarcoma cell (P > 0.05).Conclusion:Ferulic acid could significantly descend osteosarcoma cell viability through the promoting apoptosis pathway in which FA activates both caspase-3 and Bax and inactivates Bcl-2.

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“…The compound has attracted great attention due to its therapeutic activities against various diseases, such as cancer, cardiovascular and neurodegenerative diseases [157,158]. …”

Section: Experimental Studiesmentioning

confidence: 99%

“…Since the increased level of copper was observed in many cancers, and cancer cells are usually under greater oxidative stress than normal cells, the pro-oxidant ability of ferulic acid might lead to selective cytotoxicity to cancer cells [157]. Ferulic acid (10 μg/mL) also decreased cell viability and enhanced efficacy of radiotherapy in two cervical cancer cell lines (HeLa and ME-180), possibly through promotion of ROS [159].…”

Section: Experimental Studiesmentioning

confidence: 99%

Natural Polyphenols for Prevention and Treatment of Cancer

et al. 2016

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There is much epidemiological evidence that a diet rich in fruits and vegetables could lower the risk of certain cancers. The effect has been attributed, in part, to natural polyphenols. Besides, numerous studies have demonstrated that natural polyphenols could be used for the prevention and treatment of cancer. Potential mechanisms included antioxidant, anti-inflammation as well as the modulation of multiple molecular events involved in carcinogenesis. The current review summarized the anticancer efficacy of major polyphenol classes (flavonoids, phenolic acids, lignans and stilbenes) and discussed the potential mechanisms of action, which were based on epidemiological, in vitro, in vivo and clinical studies within the past five years.

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Redox cycling of endogenous copper by ferulic acid leads to cellular DNA breakage and consequent cell death: A putative cancer chemotherapy mechanism

Cited by 32 publications

References 54 publications

Synergic pro-apoptotic effects of Ferulic Acid and nanostructured lipid carrier in glioblastoma cells assessed through molecular and Delayed Luminescence studies

Synergic pro-apoptotic effects of Ferulic Acid and nanostructured lipid carrier in glioblastoma cells assessed through molecular and Delayed Luminescence studies

Ferulic acid promoting apoptosis in human osteosarcoma cell lines

Natural Polyphenols for Prevention and Treatment of Cancer

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