Luteolin inhibits proliferation, triggers apoptosis and modulates Akt/mTOR and MAP kinase pathways in HeLa cells

Raina, Ritu; Pramodh, Sreepoorna; Rais, Naushad; Haque, Shafiul; Shafarin, Jasmin; Bajbouj, Khuloud; Hamad, Mawieh; Hussain, Arif

doi:10.3892/ol.2021.12452

Cited by 42 publications

(48 citation statements)

References 58 publications

(140 reference statements)

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“…Moreover, the present study is the first to report the presence of sub‐G 1 cell cycle arrest in NPC‐BM cells after treatment with luteolin‐7‐O‐glucoside. Interestingly, some studies have reported that luteolin, a precursor compound of luteolin‐7‐O‐glucoside, regulated sub‐G 1 cell cycle arrest and apoptosis in breast, colon, and cervical cancer cells 36–38 . These findings are similar with our observation that luteolin‐7‐O‐glucoside induced sub‐G 1 cell cycle arrest in NPC‐BM cells.…”

Section: Discussionsupporting

confidence: 91%

Luteolin‐7‐O‐glucoside inhibits cell proliferation and modulates apoptosis through the AKT signaling pathway in human nasopharyngeal carcinoma

Chen

et al. 2021

Environmental Toxicology

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Nasopharyngeal carcinoma (NPC) is an unnoticeable malignant tumor with a high potential of lymphatic metastasis, and its prevalence is high in Asia. Ionizing radiation is the mainstay of treatment for patients with NPC without metastasis. However, patients with metastatic lesions require advanced treatments such as chemotherapy. The present study investigated the apoptotic effect of luteolin‐7‐O‐glucoside on NPC cells and elucidated its underlying signaling mechanisms. The results revealed that luteolin‐7‐O‐glucoside significantly reduced the proliferation of NPC cell lines (NPC‐039 and NPC‐BM). Flow cytometry and morphological analysis results demonstrated that luteolin‐7‐O‐glucoside treatment induced S and G2/M cell cycle arrest, chromatin condensation, and apoptosis. In addition, mitochondrial membrane potential was observed to be depolarized with an increasing concentration of luteolin‐7‐O‐glucoside. Proteins involved in the extrinsic and intrinsic pathways of apoptosis, such as death receptor, caspase‐3, caspase‐8, caspase‐9, and Bcl‐2 family proteins (Bax, t‐Bid, Bcl‐2, and Bcl‐xL), were downregulated and upregulated after treatment with luteolin‐7‐O‐glucoside, respectively. Moreover, the addition of a PI3K/AKT inhibitor enhanced the activation of poly‐ADP‐ribose‐polymerase (PARP) and attenuated cell viability, indicating that luteolin‐7‐O‐glucoside induced apoptosis in NPC cells through the AKT signaling pathway. These results indicated that the apoptosis of NPC cells modulated by luteolin‐7‐O‐glucoside may be preceded by mitochondrial depolarization, cell cycle arrest, extrinsic and intrinsic apoptosis pathway activation, and AKT signaling modulation. Thus, luteolin‐7‐O‐glucoside can be a promising anticancer agent against human NPC.

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Section: Discussionsupporting

confidence: 91%

Luteolin‐7‐O‐glucoside inhibits cell proliferation and modulates apoptosis through the AKT signaling pathway in human nasopharyngeal carcinoma

Chen

et al. 2021

Environmental Toxicology

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“…Modulation in expression of different proteins leads to cell growth inhibition, cell cycle arrest, DNA damage, attenuating oxidative stress and alleviating inflammation, inducing apoptosis. The current study establishes clear evidence about the multifaceted role of fisetin as an anticancer agent with its differential action towards tumour and normal cells; therefore, a safer profile [69].…”

Section: Discussionsupporting

confidence: 65%

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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“…We further focused on the DEGs in this group of genes and applied PPI network analysis to distinguish hub genes, which are defined as genes with a high degree of connectivity that play an essential role in stabilizing the PPI network structure. Here, some star genes were identified, such as RBP4 20 , SPP2 21 and MAPK3 22 , those had been confirmed a role in pathological mechanisms. Fourth, DEGs specific to CCA subtypes were explored and compared.…”

Section: Discussionmentioning

confidence: 56%

“…Out of this module, 579 DEGs were extracted and hub genes were identified through PPI network analysis. The PPI network suggested that RBP4 20 , SPP2 21 , MAPK3 22 and another around 30 genes were hub genes (Fig. 3 d).…”

Section: Resultsmentioning

confidence: 97%

A comprehensive transcriptomic landscape of cholangiocarcinoma based on bioinformatics analysis from large cohort of patients

Zhang

et al. 2021

Sci Rep

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Cholangiocarcinoma (CCA) is a group of malignancies emerging in the biliary tree and is associated with a poor patient prognosis. Although the anatomical location is the only worldwide accepted classification basis, it still has bias. The current study integrates the whole-genome expression data from several big cohorts in the literature, to screen and provide a comprehensive bioinformatic analysis, in order to better classify molecular subtypes and explore an underlying cluster mechanism related to anatomy and geographical regions. Differentially expressed protein-coding genes (DEGs) were identified for CCA as well as subtypes. Biological function enrichment analysis—Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis—was applied and identified different DEGs enriched signaling pathways in CCA subtypes. A co-expression network was presented by Weighted gene co-expression network analysis package and modules related to specific phenotypes were identified. Combined with DEGs, hub genes in the given module were demonstrated through protein–protein interaction network analysis. Finally, DEGs which significantly related to patient overall survival and disease-free survival time were selected, including ARHGAP21, SCP2, UBIAD1, TJP2, RAP1A and HDAC9.

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Luteolin inhibits proliferation, triggers apoptosis and modulates Akt/mTOR and MAP kinase pathways in HeLa cells

Cited by 42 publications

References 58 publications

Luteolin‐7‐O‐glucoside inhibits cell proliferation and modulates apoptosis through the AKT signaling pathway in human nasopharyngeal carcinoma

Luteolin‐7‐O‐glucoside inhibits cell proliferation and modulates apoptosis through the AKT signaling pathway in human nasopharyngeal carcinoma

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

A comprehensive transcriptomic landscape of cholangiocarcinoma based on bioinformatics analysis from large cohort of patients

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