Fisetin effects on cell proliferation and apoptosis in glioma cells

Pak, Fulya; Öztopçu-Vatan, Pınar

doi:10.1515/znc-2019-0098

Cited by 9 publications

(9 citation statements)

References 32 publications

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“…Here, we extended our previous study and show that, in a high concentration range, fisetin is cytotoxic on proliferating, nonsenescent cells, causing the induction of apoptosis. This confirms an early study on glioma cells (37) and other reports, demonstrating that fisetin induces apoptosis in different cancer cell lines derived from skin and ovarian cancer (38) [for review see (14)]. It was also effective in inhibiting cell migration and invasion of GBM8401 glioma cells via ERK1/2 pathway activation.…”

Section: Discussionsupporting

confidence: 88%

Genotoxic and Cytotoxic Activity of Fisetin on Glioblastoma Cells

BELTZIG,

CHRISTMANN,

DOBREANU

et al. 2024

Anticancer Res

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Background/Aim: Fisetin is a yellow-coloring flavonoid that can be found in a wide variety of plants, vegetables, and fruits, such as strawberries, apples, and grapes. It has been shown to have biological activity by targeting different pathways regulating survival and death and to bear antioxidant and anti-inflammatory activity. Fisetin was shown to be cytotoxic on different cancer cell lines and has the ability to kill therapy-induced senescent cancer cells. The aim of the study was to investigate the DNA damaging and cytotoxic potential of fisetin and its ability to enhance the killing effect of temozolomide on glioblastoma cells. Materials and Methods: We used LN229 glioblastoma cells and measured survival and apoptosis by flow cytometry, DNA strand breaks by the alkaline comet and γH2AX assay, and the DNA damage response by western blot analysis. Results: Fisetin was cytotoxic on glioblastoma cells, inducing apoptosis. In the dose range of 40-80 μM it also induced DNA damage, as measured by the alkaline comet and γH2AX assay, and triggered DNA damage response, as revealed by p53 activation. Furthermore, fisetin enhanced the genotoxic effect of methyl methanesulfonate, presumably due to inhibition of DNA repair processes. When administered together with temozolomide, the first-line therapeutic for glioblastoma, it enhanced cell death, reduced the yield of senescent cells following treatment and exhibited senolytic activity on glioblastoma cells. Conclusion: Data show that high-dose fisetin has a genotoxic potential and suggest that, harnessing the cytotoxic and senolytic activity of the flavonoid, it may enhance the effect of anticancer drugs and eliminate therapy-induced senescent cells. Therefore, it may be useful for adjuvant cancer therapy, including glioblastoma, which is worth to be studied in clinical trials.

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Section: Discussionsupporting

confidence: 88%

Genotoxic and Cytotoxic Activity of Fisetin on Glioblastoma Cells

BELTZIG,

CHRISTMANN,

DOBREANU

et al. 2024

Anticancer Res

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“…The percentage of dead cells at 20, 30 and 50 µM increased both in time and dose-dependent manner (Figure 1C). The safer profile of fisetin and other polyphenols such as quercetin, luteolin in normal cell lines and animal models was reported in other studies as well [13,29,30]. The differential cytotoxic action of fisetin towards tumour/cancer cells marks it as an ideal drug candidate.…”

Section: Discussionmentioning

confidence: 57%

Fisetin Deters Cell Proliferation, Induces Apoptosis, Alleviates Oxidative Stress and Inflammation in Human Cancer Cells, HeLa

Afroze

Pramodh

Shafarin

et al. 2022

IJMS

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Background: Fisetin, a flavonol profusely found in vegetables and fruits, exhibited a myriad of properties in preclinical studies to impede cancer growth. Purpose: This study was proposed to delineate molecular mechanisms through analysing the modulated expression of various molecular targets in HeLa cells involved in proliferation, apoptosis and inflammation. Methods: MTT assay, flow cytometry, nuclear morphology, DNA fragmentation and Annexin–Pi were performed to evaluate the anti-cancer potential of fisetin. Furthermore, qPCR and proteome profiler were performed to analyse the expression of variety of gene related to cell death, cell proliferation, oxidative stress and inflammation and cancer pathways. Results: Fisetin demonstrated apoptotic inducing ability in HeLa cells, which was quite evident through nuclear morphology, DNA ladder pattern, decreased TMRE fluorescent intensity, cell cycle arrest at G2/M and increased early and late apoptosis. Furthermore, fisetin treatment modulated pro-apoptotic genes such as APAF1, Bad, Bax, Bid and BIK at both transcript and protein levels and anti-apoptotic gene Bcl-2, BIRC8, MCL-1, XIAP/BIRC4, Livin/BIRC7, clap-2/BIRC3, etc. at protein levels to mitigate cell proliferation and induce apoptosis. Interestingly, the aforementioned alterations consequently led to an elevated level of Caspase-3, Caspase-8 and Caspase-9, which was found to be consistent with the transcript and protein level expression. Moreover, fisetin downregulated the expression of AKT and MAPK pathways to avert proliferation and enhance apoptosis of cancer cells. Fisetin treatment also improves oxidative stress and alleviates inflammation by regulating JAK-STAT/NF-kB pathways. Conclusion: Together, these studies established that fisetin deters human cervical cancer cell proliferation, enhances apoptosis and ameliorates inflammation through regulating various signalling pathways that may be used as a therapeutic regime for better cancer management.

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“…FIS was confirmed to demonstrate antiproliferative activity against glioblastoma cells, and the IC50 value was 75 µM. The presence of apoptotic changes in cells treated with FIS has also been demonstrated, and this process is time-and dose-dependent [38]. Moreover, FIS effectively inhibits migration and invasion of glioblastoma cells [39].…”

Section: Activity Toward Brain Cancer Cellsmentioning

confidence: 78%

“…FIS stably phosphorylates ERK1/2, which contributes to the inhibition of ADAM9 protein expression [39]. FIS increases the expression of caspase-3 and 9 and BAX protein, while reducing the expression of the anti-apoptotic protein BCL-2 and survivin [38]. Examination of the activation of the ERK1/2 and Akt signaling pathways found that FIS significantly induces the phosphorylation of ERK1/2 expression.…”

Section: Activity Toward Brain Cancer Cellsmentioning

confidence: 99%

“…-induced cell invasion in MCF-7 cells FIS inhibits the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways[35] MCF-7 ≈40 * FIS exhibits substantial cytotoxicity in caspase-3-deficient MCF-7 cells FIS does not induce necroptosis in MCF-7 cells FIS induces caspase-dependent cell death in MCF-7 cells FIS induces mitochondrial depolarization and p53-independent cell death in MCF-7 cells FIS inhibits autophagy in MCFinhibition of cell migration and inhibits the invasion of GBM8401 cells FIS inhibits the expression of ADAM9 protein and mRNA FIS phosphorylates ERK1/2 in a sustained way expression of caspase-3, caspase-9, caspase-8, and bax FIS downregulates the expression of Bcl-2 and survivin[38] Cervix HeLa ND FIS induces morphological changes and inhibits proliferation FIS changes nuclear morphology FIS leads DNA fragmentation FIS encourages G2/M arrest and modulates cell-cycle regulatory genes FIS activates extrinsic and intrinsic pathways FIS modulates expression of various pro-and anti-apoptotic proteins FIS elevates caspase-3, caspase-8 and caspase-9 activity FIS changes the aberrant MAPK and PI3K/AKT/mTOR in HeLa cells of HeLa cells in a dose-and time-dependent manner FIS triggers the activations of caspases-3 and -8 and the cleavages of poly (ADP-ribose) polymerase FIS induces a sustained activation of the phosphorylation of ERK1/2 FIS significantly reduces tumor growth in mice with HeLa tumor xenografts[44] …”

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confidence: 99%

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Fisetin, a Potent Anticancer Flavonol Exhibiting Cytotoxic Activity against Neoplastic Malignant Cells and Cancerous Conditions: A Scoping, Comprehensive Review

et al. 2022

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Diet plays a crucial role in homeostasis maintenance. Plants and spices containing flavonoids have been widely used in traditional medicine for thousands of years. Flavonols present in our diet may prevent cancer initiation, promotion and progression by modulating important enzymes and receptors in signal transduction pathways related to proliferation, differentiation, apoptosis, inflammation, angiogenesis, metastasis and reversal of multidrug resistance. The anticancer activity of fisetin has been widely documented in numerous in vitro and in vivo studies. This review summarizes the worldwide, evidence-based research on the activity of fisetin toward various types of cancerous conditions, while describing the chemopreventive and therapeutic effects, molecular targets and mechanisms that contribute to the observed anticancer activity of fisetin. In addition, this review synthesized the results from preclinical studies on the use of fisetin as an anticancer agent. Based on the available literature, it might be suggested that fisetin has a bioactive potential to become a complementary drug in the prevention and treatment of cancerous conditions. However, more in-depth research is required to validate current data, so that this compound or its derivatives can enter the clinical trial phase.

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Fisetin effects on cell proliferation and apoptosis in glioma cells

Cited by 9 publications

References 32 publications

Genotoxic and Cytotoxic Activity of Fisetin on Glioblastoma Cells

Genotoxic and Cytotoxic Activity of Fisetin on Glioblastoma Cells

Fisetin Deters Cell Proliferation, Induces Apoptosis, Alleviates Oxidative Stress and Inflammation in Human Cancer Cells, HeLa

Fisetin, a Potent Anticancer Flavonol Exhibiting Cytotoxic Activity against Neoplastic Malignant Cells and Cancerous Conditions: A Scoping, Comprehensive Review

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