Gossypetin, a naturally occurring hexahydroxy flavone, ameliorates gamma radiation-mediated DNA damage

Khan, Amitava; Manna, Krishnendu; Bose, Chinchu; Sinha, Mahuya; Das, Dipesh; Kesh, Swaraj Bandhu; Chakrabarty, Anindita; Banerji, Asoke; Dey, Sanjit

doi:10.3109/09553002.2013.811310

Cited by 37 publications

(38 citation statements)

References 49 publications

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“…The compound GTIN was not fully explored so far in terms of its biological effects. Previous studies have showed that GTIN prevented allergic reaction, possessed antimicrobial activity, and ameliorated gamma radiation‐mediated DNA damage . GTIN has been shown to be quite effective in suppressing N‐methyl‐N′‐nitro‐N′‐nitrosoguanidine (MNNG) mutagenicity, exhibiting as much as 70% inhibition .…”

Section: Introductionmentioning

confidence: 99%

Anti‐prostate cancer potential of gossypetin via inducing apoptotic and autophagic cell death

Lee

Tsai

Wang

et al. 2017

Molecular Carcinogenesis

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Gossypetin (GTIN), a naturally occurring hexahydroxy flavone, has been shown to possess antimutagenic, antioxidant, antimicrobial, and antiatherosclerotic effects. Here, we investigated the mechanism(s) underlying the anticancer potential of GTIN. In this study, investigations were showed that GTIN preferentially induces programed cell death of prostate cancer (PCa) cells in vitro and in vivo. MTT data showed that GTIN exhibited the anti-proliferation effect on human PCa cells in a dose- and time-dependent manner. Among two kinds of PCa cells, androgen-dependent LNCaP cells were the most susceptible to GTIN. GTIN was evaluated for apoptotic and autophagic activities in LNCaP cells, but not in androgen-independent DU145 cells with mutant Atg5 and resistant to autophagy. Molecular data showed the apoptotic effect of GTIN at a high dose in PCa cells might be mediated via mitochondrial pathway. The lower dose of GTIN-induced autophagy enhances LNCaP cell death, and is dependent on class III PI3K and Atg5 pathway. Finally, GTIN was evidenced by its inhibition on the growth of LNCaP cells in xenograft tumor studies. As a result, our data presented the first evidence of GTIN as an inducer of apoptotic and autophagic cell death in LNCaP cells, and provide a new mechanism for its anticancer activity.

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Section: Introductionmentioning

confidence: 99%

Anti‐prostate cancer potential of gossypetin via inducing apoptotic and autophagic cell death

Lee

Tsai

Wang

et al. 2017

Molecular Carcinogenesis

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“…Multiple lines of evidence have shown that γ-radiation exposure can induce a variety of cellular and sub-cellular damage in many living organisms at sub-lethal doses, including genomic instability, mutagenesis, and cell death (Garrison and Uyeki 1988). During radiotherapy, γ-irradiation interacts with biological systems to produce free radicals, such as hydroxyl radicals (•OH), that are formed from the radiolysis of surrounding water molecules and successively attack DNA (Khan et al 2013). Importantly, γ-radiation can be absorbed directly by DNA, thereby leading to ionization of both nucleobases and sugars in a mechanism described as the direct effect of the generation of single and tandem DNA damage (Rezaee et al 2013).…”

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confidence: 99%

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage

Chen

Liu

Dong

et al. 2015

Cell Stress and Chaperones

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Radiation-induced cellular injury is attributed primarily to the harmful effects of free radicals, which play a key role in irradiation-induced apoptosis. In this study, we investigated the radioprotective efficacy of edaravone, a licensed clinical drug and a powerful free radical scavenger that has been tested against γ-irradiation-induced cellular damage in cultured human peripheral blood lymphocytes in studies of various diseases. Edaravone was pre-incubated with lymphocytes for 2 h prior to γ-irradiation. It was found that pretreatment with edaravone increased cell viability and inhibited generation of γ-radiation-induced reactive oxygen species (ROS) in lymphocytes exposed to 3 Gy γ-radiation. In addition, γ-radiation decreased antioxidant enzymatic activity, such as superoxide dismutase and glutathione peroxidase, as well as the level of reduced glutathione. Conversely, treatment with 100 μM edaravone prior to irradiation improved antioxidant enzyme activity and increased reduced glutathione levels in irradiated lymphocytes. Importantly, we also report that edaravone reduced γ-irradiation-induced apoptosis through downregulation of Bax, upregulation of Bcl-2, and consequent reduction of the Bax:Bcl-2 ratio. The current study shows edaravone to be an effective radioprotector against γ-irradiation-induced cellular damage in lymphocytes in vitro. Finally, edaravone pretreatment significantly reduced DNA damage in γ-irradiated lymphocytes, as measured by comet assay (% tail DNA, tail length, tail moment, and olive tail moment) (p<0.05). Thus, the current study indicates that edaravone offers protection from radiation-induced cytogenetic alterations.

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“…1 ). This compound list included several well reported bio-active hydroxylated flavones such as fisetin [ 15 ], quercetin [ 4 , 5 ], morin [ 2 ], tricetin [ 15 ], gossypetin [ 16 ], apigenin [ 2 , 4 ] and myricetin [ 2 ], which exhibit broad spectrum anti-inflammatory and anticancer effects.…”

Section: Resultsmentioning

confidence: 99%

6-Hydroxyflavone and Derivatives Exhibit Potent Anti-Inflammatory Activity among Mono-, Di- and Polyhydroxylated Flavones in Kidney Mesangial Cells

Wang

Sidhu

et al. 2015

PLoS ONE

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Inflammatory responses by kidney mesangial cells play a critical role in the glomerulonephritis. The anti-inflammatory potential of nineteen mono-, di- and polyhydroxylated flavones including fisetin, quercetin, morin, tricetin, gossypetin, apigenin and myricetin were investigated on rat mesangial cells with lipopolysaccharide (LPS) as the inflammatory stimuli. 6-Hydroxyflavone and 4′,6-dihydroxyflavone exhibited high activity with IC50 in the range of 2.0 μM, a much better inhibition potential in comparison to the well-studied polyhydroxylated flavones. Interestingly, the anti-inflammatory activity was not due to direct quenching of NO radicals. Investigation on derivatives with methylation, acetylation or sulfation of 6-hydroxyl group revealed that 6-methoxyflavone was the most potent with an IC50 of 192 nM. Mechanistic study indicated that the anti-inflammatory activity of 6-methoxyflavone arose via the inhibition of LPS-induced downstream inducible NO synthase in mesangial cells. The identification of 6-hydroxyflavone and 6-methoxyflavone with potent anti-inflammatory activity in kidney mesangial cells provides a new flavone scaffold and direction to develop naturally derived products for potential nephritis prevention and treatment.

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Gossypetin, a naturally occurring hexahydroxy flavone, ameliorates gamma radiation-mediated DNA damage

Abstract: GTIN ameliorated radiation-induced oxidative stress and DNA damage by its free-radical scavenging activity.

Cited by 37 publications

References 49 publications

Anti‐prostate cancer potential of gossypetin via inducing apoptotic and autophagic cell death

Anti‐prostate cancer potential of gossypetin via inducing apoptotic and autophagic cell death

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage

6-Hydroxyflavone and Derivatives Exhibit Potent Anti-Inflammatory Activity among Mono-, Di- and Polyhydroxylated Flavones in Kidney Mesangial Cells

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