Cytotoxicity of apigenin toward multiple myeloma cell lines and suppression of iNOS and COX-2 expression in STAT1-transfected HEK293 cells

Adham, Aveen Nozad; Abdelfatah, Sara; Naqishbandi, Alaadin M.; Mahmoud, Nuha; Efferth, Thomas

doi:10.1016/j.phymed.2020.153371

Cited by 68 publications

(45 citation statements)

References 65 publications

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“…As tumor suppressor, apigenin has the ability to inhibit tumor growth via the promotion of cell-cycle arrest, apoptosis and autophagy, preventing tumor cell proliferation, migration and invasion [ 69 ]. In Adham’s study, apigenin triggered cell death through ferroptosis in NCI-H929 cells [ 70 ]. However, apigenin has dual characters, which can inhibit ferroptosis in some case.…”

Section: Natural Bioactive Compounds As Ferroptosis Regulatorsmentioning

confidence: 99%

The Regulatory Effects and the Signaling Pathways of Natural Bioactive Compounds on Ferroptosis

Zhang

Geng

et al. 2021

Foods

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Natural bioactive compounds abundantly presented in foods and medicinal plants have recently received a remarkable attention because of their various biological activities and minimal toxicity. In recent years, many natural compounds appear to offer significant effects in the regulation of ferroptosis. Ferroptosis is the forefront of international scientific research which has been exponential growth since the term was coined. This type of regulated cell death is driven by iron-dependent phospholipid peroxidation. Recent studies have shown that numerous organ injuries and pathophysiological processes of many diseases are driven by ferroptosis, such as cancer, arteriosclerosis, neurodegenerative disease, diabetes, ischemia-reperfusion injury and acute renal failure. It is reported that the initiation and inhibition of ferroptosis plays a pivotal role in lipid peroxidation, organ damage, neurodegeneration and cancer growth and progression. Recently, many natural phytochemicals extracted from edible plants have been demonstrated to be novel ferroptosis regulators and have the potential to treat ferroptosis-related diseases. This review provides an updated overview on the role of natural bioactive compounds and the potential signaling pathways in the regulation of ferroptosis.

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Section: Natural Bioactive Compounds As Ferroptosis Regulatorsmentioning

confidence: 99%

The Regulatory Effects and the Signaling Pathways of Natural Bioactive Compounds on Ferroptosis

Zhang

Geng

et al. 2021

Foods

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“…The available literature demonstrated that flavonoids and terpenoids are abundant in vegetables, fruits, and medicinal herbs and revealed cytotoxicity towards several human cancer cell lines and induced cell death through various mechanisms [36]. A recent study reported that in MM cells, apigenin treatment potently inhibited cell development in a concentration-dependent manner by inducing cell apoptosis, ferroptosis, and autophagy, associated with down-regulating of STAT1, and Akt with concomitant activation of caspases, JNK, P-38 MAPK, Beclin-1, and LC3 II [37]. In human papillary thyroid carcinoma BCPAP cells, apigenin induced G2/M cell cycle arrest and DNA damage through suppressing the expression of Cdc25c and triggering the accumulation of ROS production [38].…”

Section: Discussionmentioning

confidence: 99%

Induction of Apoptosis, Autophagy and Ferroptosis by Thymus vulgaris and Arctium lappa Extract in Leukemia and Multiple Myeloma Cell Lines

2020

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Thymus vulgaris and Arctium lappa have been used as a folk remedy in the Iraqi Kurdistan region to deal with different health problems. The aim of the current study is to investigate the cytotoxicity of T. vulgaris and A. lappa in leukemia and multiple myeloma (MM) cell lines and determine the mode of cell death triggered by the most potent cytotoxic fractions of both plants in MM. Resazurin assay was used to evaluate cytotoxic and ferroptosis activity, apoptosis, and modulation in the cell cycle phase were investigated via Annexin V-FITC/PI dual stain and cell-cycle arrest assays. Furthermore, we used western blotting assay for the determination of autophagy cell death. n-Hexane, chloroform, ethyl acetate, and butanol fractions of T. vulgaris and A. lappa exhibited cytotoxicity in CCRF-CEM and CEM/ADR 5000 cell lines at concentration range 0.001–100 μg/mL with potential activity revealed by chloroform and ethyl acetate fractions. NCI-H929 displayed pronounced sensitivity towards T. vulgaris (TCF) and A. lappa (ACF) chloroform fractions with IC50 values of 6.49 ± 1.48 and 21.9 ± 0.69 μg/mL, respectively. TCF induced apoptosis in NCI-H929 cells with a higher ratio (71%), compared to ACF (50%) at 4 × IC50. ACF demonstrated more potent autophagy activity than TCF. TCF and ACF induced cell cycle arrest and ferroptosis. Apigenin and nobiletin were identified in TCF, while nobiletin, ursolic acid, and lupeol were the main compounds identified in ACF. T. vulgaris and A. lappa could be considered as potential herbal drug candidates, which arrest cancer cell proliferation by induction of apoptosis, autophagic, and ferroptosis.

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“…Zhou et al have also shown that apigenin has antiproliferative, anti-migration, and anti-invasive effects on human lung carcinoma cells A549 by targeting the PI3K/Akt signaling pathway [ 394 ]. Recently, in [ 395 ], it was found that apigenin may be an appropriate candidate for the treatment of multiple myeloma due to its inhibition of the STAT1/COX-2/iNOS signaling pathway, which is an important mechanism not only for suppressing inflammation, but also for the apoptosis induction. It was reported that by reducing the level of proinflammatory cytokines, apigenin suppressed inflammation and inflammation-induced carcinogenesis in colon cells by regulating the activity of NF-κB and STAT3 [ 396 ], and also greatly reduced TNFa levels in the MDA-MB-231 TNBC cell line [ 397 ].…”

Section: Natural Compounds and Important Targets Associated With Chronic Inflammation And Oxidative Stress In Cancer Treatmentmentioning

confidence: 99%

Therapeutic Influence on Important Targets Associated with Chronic Inflammation and Oxidative Stress in Cancer Treatment

Neganova

Liu

Aleksandrova

et al. 2021

Cancers

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Chronic inflammation and oxidative stress are the interconnected pathological processes, which lead to cancer initiation and progression. The growing level of oxidative and inflammatory damage was shown to increase cancer severity and contribute to tumor spread. The overproduction of reactive oxygen species (ROS), which is associated with the reduced capacity of the endogenous cell defense mechanisms and/or metabolic imbalance, is the main contributor to oxidative stress. An abnormal level of ROS was defined as a predisposing factor for the cell transformation that could trigger pro-oncogenic signaling pathways, induce changes in gene expression, and facilitate accumulation of mutations, DNA damage, and genomic instability. Additionally, the activation of transcription factors caused by a prolonged oxidative stress, including NF-κB, p53, HIF1α, etc., leads to the expression of several genes responsible for inflammation. The resulting hyperactivation of inflammatory mediators, including TNFα, TGF-β, interleukins, and prostaglandins can contribute to the development of neoplasia. Pro-inflammatory cytokines were shown to trigger adaptive reactions and the acquisition of resistance by tumor cells to apoptosis, while promoting proliferation, invasion, and angiogenesis. Moreover, the chronic inflammatory response leads to the excessive production of free radicals, which further aggravate the initiated reactions. This review summarizes the recent data and progress in the discovery of mechanisms that associate oxidative stress and chronic inflammation with cancer onset and metastasis. In addition, the review provides insights for the development of therapeutic approaches and the discovery of natural substances that will be able to simultaneously inhibit several key oncological and inflammation-related targets.

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Cytotoxicity of apigenin toward multiple myeloma cell lines and suppression of iNOS and COX-2 expression in STAT1-transfected HEK293 cells

Cited by 68 publications

References 65 publications

The Regulatory Effects and the Signaling Pathways of Natural Bioactive Compounds on Ferroptosis

The Regulatory Effects and the Signaling Pathways of Natural Bioactive Compounds on Ferroptosis

Induction of Apoptosis, Autophagy and Ferroptosis by Thymus vulgaris and Arctium lappa Extract in Leukemia and Multiple Myeloma Cell Lines

Therapeutic Influence on Important Targets Associated with Chronic Inflammation and Oxidative Stress in Cancer Treatment

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