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 58 publications

(36 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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“…Apigenin impairs progression of multiple myeloma cells in a dose-dependent manner. Apigenin is able to down-regulate STAT1 expression in suppressing COX-2/iNOS axis [ 131 ]. A combination of apigenin and hesperidin prevent DNA repair in breast tumor to potentiate DOX activity in cancer suppression [ 132 ].…”

Section: Dietary Agents and Cancer Stem Cellsmentioning

confidence: 99%

Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies

Paskeh

Asadi²,

Zabolian

et al. 2021

IJMS

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As a multifactorial disease, treatment of cancer depends on understanding unique mechanisms involved in its progression. The cancer stem cells (CSCs) are responsible for tumor stemness and by enhancing colony formation, proliferation as well as metastasis, and these cells can also mediate resistance to therapy. Furthermore, the presence of CSCs leads to cancer recurrence and therefore their complete eradication can have immense therapeutic benefits. The present review focuses on targeting CSCs by natural products in cancer therapy. The growth and colony formation capacities of CSCs have been reported can be attenuated by the dietary agents. These compounds can induce apoptosis in CSCs and reduce tumor migration and invasion via EMT inhibition. A variety of molecular pathways including STAT3, Wnt/β-catenin, Sonic Hedgehog, Gli1 and NF-κB undergo down-regulation by dietary agents in suppressing CSC features. Upon exposure to natural agents, a significant decrease occurs in levels of CSC markers including CD44, CD133, ALDH1, Oct4 and Nanog to impair cancer stemness. Furthermore, CSC suppression by dietary agents can enhance sensitivity of tumors to chemotherapy and radiotherapy. In addition to in vitro studies, as well as experiments on the different preclinical models have shown capacity of natural products in suppressing cancer stemness. Furthermore, use of nanostructures for improving therapeutic impact of dietary agents is recommended to rapidly translate preclinical findings for clinical use.

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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 58 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

Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies

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