Gardenin B-induced cell death in human leukemia cells involves multiple caspases but is independent of the generation of reactive oxygen species

Cabrera, Javier; Saavedra, Ester; Rosario, Henoc del; Perdomo, Juan Alejandro; Loro-Ferrer, Juan Francisco; Cifuente, Diego Alberto; Tonn, Carlos E.; García, Celina; Quintana, José; Estévez, Francisco

doi:10.1016/j.cbi.2016.07.016

Cited by 18 publications

(11 citation statements)

References 36 publications

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“…Interestingly, our data show that GB can induce caspase-3 activities in Drosophila heads. In support of our findings, GB has been shown to induce caspase-dependent apoptosis in human leukemia cell lines 76 . Future studies will be directed towards exploring the structural features of flavonoids that are critical for modulation of caspase activities in PD models.…”

Section: Discussionsupporting

confidence: 90%

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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Section: Discussionsupporting

confidence: 90%

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

Maitra

Harding

Liang

et al. 2020

Preprint

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“…Besides, antileukemic function of flavonoids, for example, baicalein and myricetin in CML (Romanouskaya & Grinev, 2009), alvocidib (Zeidner & Karp, 2015) and catechin (Mukhopadhyay, Shaw, & Nath, 2017) in AML, chrysin in CLL (Salimi et al, 2017), and wogonoside in T-cell ALL (T-ALL; R. Xiao, Gan, & Jiang, 2017) has demonstrated. activation and significantly increased PARP rate, a member of a family of intracellular proteins, which has important role in DNA repair and activity (Cabrera et al, 2016). Likewise, in flavonoidtreated Kasumi-1 cells, leukemic cell line with an 8; 21 chromosome translocation, activated form of caspase 3, 9, and PARP improved meaningfully, and consequently apoptosis rate of target cells augmented noticeably (B.…”

Section: Flavonoids: Leukemia Therapymentioning

confidence: 97%

“…In the below (Table ), we have cited some of the very noteworthy flavonoids, such as quercetin (X. X. Chen et al, ; G. L. Russo et al, ), luteolin (Sak et al, ), gardenin B (Cabrera et al, ), hespertin and fisetin (Adan & Baran, ), myricetin (Ko et al, ), wogonin (H. W. Zhang et al, ), flavopiridol (Bright et al, ), vitexin inspired (Ling et al, ), sophoraflavanone G (Z. Y. Li et al, ), flavokawin B (Tang et al, ), kaempferol (K. Y. Kim et al, ), chrysin (Zaric et al, ), butein (Woo et al, ), naringenin (R. F. Li et al, ), catechin (L. Zhang et al, ), genistein (I. G. Kim et al, ), apigenin (Gonzalez‐Mejia et al, ; Jayasooriya et al, ), dorsmanin F (Kuete et al, ), astilbin (H. W. Yi et al, ), EGCG (Annabi et al, ; J. H. Jung et al, ), icaraside (Kang et al, ), phloridzin (Arumuggam et al, ), isochamaejasmin (S. D. Zhang et al, ), MF derivatives (Wudtiwai et al, ), icaritin (Q. Li et al, ), FEOJ (W. S. Lee et al, ), casticin (Kikuchi et al, ), chalcone (Mori et al, ), deguelin (S. Yi et al, ), morin (C. Park et al, ), medicarpin (Gatouillat et al, ), Antho 50 (Alhosin et al, ), rotenone (Estrella‐Parra et al, ), glabridin (H. L. Huang et al, ), hispidulin (H. Gao et al, ), oroxylin A (Hui et al, ), rhamnazin (Philchenkov & Zavelevych, ), wogonoside (Y. Chen et al, ), 7,8‐dihydroxyflavone hydrate (7,8‐DHF; H. Y. Park et al, ), panduratin A (Choi, Kim, & Hwang, ), silibinin (Pesakhov, Khanin, Studzinski, & Danilenko, ), galangin (Tolomeo et al, ), 2′‐nitroflavone (Cardenas, Blank, Marder, & Roguin, ), propolis (Eom, Lee, Yoon, & Yoo, ), tomentodiplacone B (Kollar, Barta, Zavalova, Smejkal, & Hampl, ), tamarixetin (Nicolini et al, ), phloretin (Kobori, Iwashita, Shinmoto, & Tsushida, ), a...…”

Section: Flavonoids Functional Mechanisms In Leukemia Cellsmentioning

confidence: 99%

“…In the below (Table 1), we have cited some of the very noteworthy flavonoids, such as quercetin (X. X. G. L. Russo et al, 2014), luteolin (Sak et al, 2016), gardenin B (Cabrera et al, 2016), hespertin and fisetin (Adan & Baran, 2015), myricetin (Ko et al, 2005), wogonin (H. W. Zhang et al, 2008), flavopiridol (Bright et al, 2010), vitexin inspired (Ling et al, 2018), sophoraflavanone G (Z. Y. Li et al, 2016), flavokawin B , kaempferol (K. Y.…”

Section: Inhibition Of Survival Involved Signaling Pathwaysmentioning

confidence: 99%

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Leukemia therapy by flavonoids: Future and involved mechanisms

Saraei

Marofi

Naimi

et al. 2018

Journal Cellular Physiology

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Flavonoids are a varied family of phytonutrients (plant chemicals) usually are detected in fruits and vegetables. In this big family, there exist more than 10,000 members that is separated into six chief subtypes: isoflavonols, flavonoenes, flavones, flavonols, anthocyanins, and chalcones. The natural compounds, such as fruits, have visible positive effects in regulating of survival involved signaling pathways that performance as the regulator of cell survival, growth, and proliferation. Researchers have established that commonly consumption up flavonoids decreases incidence and development risk of certain cancers, especially leukemia. Flavonoids have been able to induce apoptosis and stimulate cell cycle arrest in cancer cells via different pathways. Similarly, they have antiangiogenesis and antimetastasis capability, which were shown in wide ranges of cancer cells, particularly, leukemia. It seems that flavonoid because of their widespread approval, evident safety and low rate of side effects, have hopeful anticarcinogenic potential for leukemia therapy. Based on the last decade reports, the most important acting mechanisms of these natural compounds in leukemia cells are stimulating of apoptosis pathways by upregulation of caspase 3, 8, 9 and poly ADP‐ribose polymerase (PARP) and proapoptotic proteins, particularly Bax activation. As well, they can induce cell cycle arrest in target cells not only via increasing of activated levels of p21 and p53 but also by inhibition of cyclins and cyclin‐dependent kinases. Furthermore, attenuation of neclear factor‐κB and signal transducer and activator of transcription 3 activation, suppression of signaling pathway and downregulation of intracellular antiapoptotic proteins are other significant antileukemic function mechanism of flavonoids. Overall, it appears that flavonoids are promising and effective compounds in the field of leukemia therapy. In this review, we tried to accumulate and revise most promising flavonoids and finally declared their major working mechanisms in leukemia cells.

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“…Medium doses of SO extract induced apoptosis comarable to capecitabine as one of the standard agents of colorectal cancer chemotherapy. Considering above mentioned facts, it seems SO extract could induce apoptosis by acaspace 3 independent pathways [30][31][32].…”

Section: Discussionmentioning

confidence: 93%

Apoptosis and Caspase 3 Pathway Role on Anti-Proliferative Effects of Scrophulariaoxy Sepala Methanolic Extract on Caco-2 Cells

et al. 2017

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Colorectal cancer is one the most important malignancies worldwide and finding new treatment option for this cancer is of high priority. Natural compounds are common source of drugs for treatment of various diseases including cancers. The aim of this study was to investigate the effects of Scrophularia oxysepala extract on Caco-2 cells and explore the possible role of caspase 3 pathway in inducing cell death in this cancer cells in compare with chemotherapy agents of cisplatin and capecitabine. The methanolic extract of Scrophularia oxysepala (SO) was prepared by drench method. The IC50 of extract, cisplatin and capecitabine on Caco-2 cells were determined by MTT assay. The effect of SO extract on caspase 3 expression and inducing apoptosis were determined using TUNEL assay and caspase 3 ELISA methods, respectively. The IC50 of SO extract, cisplatin and capecitabine were 300, 195 and 80 µg/ml, respectively. Analysis for apoptosis revealed that SO methanolic extract increased apoptosis significantly (P<0.001) compared with control group. The effect of high doses of SO extract on apoptosis induction were comparable to cisplatin but significantly were higher than capecitabine. Only high doses of SO methanolic extract showed significant effects (P<0.05) on increasing caspase 3 compared to control group. The methanolic extract of SO showed inhibitory effect on Caco-2 cells and induced apoptosis in a dose-dependent manner comparable to cisplatin and higher than capecitabine 2 commonly used chemotherapeutic agent for various cancers.

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Gardenin B-induced cell death in human leukemia cells involves multiple caspases but is independent of the generation of reactive oxygen species

Cited by 18 publications

References 36 publications

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

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

Leukemia therapy by flavonoids: Future and involved mechanisms

Apoptosis and Caspase 3 Pathway Role on Anti-Proliferative Effects of Scrophulariaoxy Sepala Methanolic Extract on Caco-2 Cells

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