Some natural flavonoids are competitive inhibitors of caspase-1, -3, and -7 despite their cellular toxicity

White, Brandon; Beckford, Jeremy; Yadegarynia, Sina; Ngo, Nhi; Lialiutska, Tetiana; d’Alarcao, Marc

doi:10.1016/j.foodchem.2011.10.026

Cited by 35 publications

(25 citation statements)

References 27 publications

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“…Some authors suggest that apoptosis, induced in tumor cells by flavonoids, is not realized by caspase [26]. However, most authors think that flavonoids activate caspase 3 [4,27,28].…”

Section: Discussionmentioning

confidence: 99%

The apoptotic activity of flavonoid-containing Gratiola officinalis extract in cell cultures of human kidney cancer

Polukonova¹,

Navolokin²,

Bucharskaya³

et al. 2018

Russ Open Med J

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Objective -The discovery of the apoptosis-inducing effects of flavonoid vagonin allowed to make an assumption of existence of similar effect in others flavonoids. This study is devoted to the effects of Gratīola officinālis extract on cell culture of the human kidney cancer.Methods -Cell cultures of human kidney carcinoma -Caki-1 and SN12c were used in the study. The cells were stained with Hoechat 33258 dye. The number of living cells, cells in a state of apoptosis and mitosis were counted. The Cramer-Welch criterion (T) was used to compare the obtained data.Results -The activation of apoptosis was noted at all concentrations of the Gratiola officinalis L. extract during the first day of exposure. The apoptotic activity increased with increasing of extract concentration. After 48 hours, this activity was maintained only at a Gratiola officinalis L. extract concentration of 0.9 mg/ml. After 24 hours, the apoptotic activity of the extract was more expressed in the culture of CaKi-1. However, after 48 hours the extract induces more pronounced apoptosis in the culture of Sn12c cells. The cytotoxic activity of the extract was not differ after 24 hours in both cultures, after 48 hours it was more pronounced in the culture of CaKi-1. Conclusion -We revealed a pronounced antitumor and apoptotic activity of the Gratiola officinalis L. extract against the cultures of the kidney cancer Caki-1 and Sn12c. Apoptosis of tumor cells can be manifested in the form of pycnosis of the nucleus, the formation of apoptotic bodies and the emergence of cellular debris resulting from complete degradation of tumor cells. The apoptotic activity of the Gratiola officinalis extract depends on their concentration.

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“…Some authors suggest that apoptosis, induced in tumor cells by flavonoids, is not realized by caspase [26]. However, most authors think that flavonoids activate caspase 3 [4,27,28].…”

Section: Discussionmentioning

confidence: 99%

The apoptotic activity of flavonoid-containing Gratiola officinalis extract in cell cultures of human kidney cancer

Polukonova¹,

Navolokin²,

Bucharskaya³

et al. 2018

Russ Open Med J

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“…Caspase activation appears to be involved in the progressive demise of the dopaminergic neurons resulting in PD pathogenesis. Previous studies have shown that flavonoids can function as specific activators or inhibitors of caspases 44,45 . Inhibitors against different caspases have been shown to rescue neuronal deaths in several experimental PD models 41,73 .…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, caspase inhibition has been shown to alleviate dopaminergic neuronal death in mammalian PD models. Flavonoids are known to regulate apoptotic pathways in both in vitro and in vivo disease models, including NDs 44,45 . Therefore, we aimed to determine the effects of GA and GB on the activation of caspase-3 responsible for inducing apoptotic cell death.…”

Section: Differential Regulation Of Caspase-dependent Cellular Death mentioning

confidence: 99%

GardeninA confers neuroprotection against environmental toxin in aDrosophilamodel of Parkinson’s disease

Maitra

Harding

Liang

et al. 2020

Preprint

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Parkinson's disease (PD) is an age-associated neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons from the midbrain. Epidemiological studies have implicated exposures to environmental toxins like the herbicide, paraquat (PQ) as major contributors to PD etiology in both mammalian and invertebrate models. We have employed a PQinduced PD model in Drosophila as an inexpensive in vivo platform to screen therapeutics from natural products. We have identified the polymethoxyflavonoid, GardeninA, with neuroprotective potential against PQ-induced parkinsonian symptoms involving reduced survival, mobility defects, and loss of dopaminergic neurons. GardeninA-mediated neuroprotection is not solely dependent on its antioxidant activities but also involves modulation of the neuroinflammatory and cellular death responses. Furthermore, we have successfully detected GardeninA bioavailability in the fly heads after oral administration using ultra-performance liquid chromatography and mass spectrometry. Our findings reveal a molecular mechanistic insight into GardeninA-mediated neuroprotection against environmental toxin-induced PD pathogenesis for novel therapeutic intervention.

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“…Flavonoids have been demonstrated to exhibit anti-inflammatory, -allergic, -oxidative, -damage and -tumour effects (17,18). In recent years, studies on flavonoids have entered a new phase with these compounds revealed to inhibit proliferation of cancer cells, including breast, colon, lung, cervical and liver cancers and lymphoma cells (19)(20)(21)(22)(23). In addition, alpinetin has also been identified to inhibit proliferation of leukemic cells (24).…”

Section: Discussionmentioning

confidence: 99%

Alpinetin promotes Bax translocation, induces apoptosis through the mitochondrial pathway and arrests human gastric cancer cells at the G2/M phase

Wang

Lü

et al. 2012

Molecular Medicine Reports

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Abstract. Alpinetin is a natural flavonoid widely distributed inZingiberaceae. Previous studies have demonstrated that alpinetin markedly inhibits tumour growth. However, the molecular mechanisms underlying the antitumour effects of alpinetin are unclear. Bcl-2-associated X protein (Bax) translocation is known to activate the mitochondrial-dependent endogenous apoptosis pathway. The aim of the current study was to investigate the roles of Bax and the mitochondrial pathway during alpinetin-induced gastric cancer cell apoptosis and the effects of alpinetin on the cell cycle. Human gastric cancer cells were treated with various doses of alpinetin and an MTT assay was performed to measure cell viability, flow cytometry to measure the apoptotic rate, changes in the cell cycle and mitochondrial membrane potential and western blot analysis to detect the expression levels of relevant proteins. Results demonstrate that alpinetin induces apoptosis in human gastric cancer cells in a dose-and time-dependent manner. During the early stages of apoptosis, alpinetin may alter mitochondrial membrane potential leading to release of cytochrome c from mitochondria, activation of caspase family members and ultimately apoptosis of human gastric cancer cells. Results of the present study indicate that alpinetin-induced human gastric cancer cell apoptosis is associated with the mitochondrial pathway.

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Some natural flavonoids are competitive inhibitors of caspase-1, -3, and -7 despite their cellular toxicity

Cited by 35 publications

References 27 publications

The apoptotic activity of flavonoid-containing Gratiola officinalis extract in cell cultures of human kidney cancer

The apoptotic activity of flavonoid-containing Gratiola officinalis extract in cell cultures of human kidney cancer

GardeninA confers neuroprotection against environmental toxin in aDrosophilamodel of Parkinson’s disease

Alpinetin promotes Bax translocation, induces apoptosis through the mitochondrial pathway and arrests human gastric cancer cells at the G2/M phase

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