The Anticancer Effects of Flavonoids through miRNAs Modulations in Triple-Negative Breast Cancer

Adinew, Getnet Mequanint; Taka, Equar; Mendonca, Patricia; Messeha, Samia S.; Soliman, Karam F.A.

doi:10.3390/nu13041212

Cited by 40 publications

(25 citation statements)

References 353 publications

(358 reference statements)

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“…TQ has been studied in in vitro and in vivo models for its antioxidant, anti-inflammatory, and anti-cancer properties [ 19 ]. Recently, myriads of research demonstrated the anticancer effect of TQ on several types of cancer, including breast, ovarian, larynx, colon, myeloblastic leukemia, osteosarcoma, and lung cancer [ 20 , 21 ]. Anti-proliferation, apoptosis induction, cell cycle arrest, and anti-metastasis/anti-angiogenesis are crucial mechanisms employed by TQ against cancer [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Thymoquinone Alterations of the Apoptotic Gene Expressions and Cell Cycle Arrest in Genetically Distinct Triple-Negative Breast Cancer Cells

et al. 2022

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Breast cancer (BC) is the most common cancer in women worldwide, and it is one of the leading causes of cancer death in women. triple-negative breast Cancer (TNBC), a subtype of BC, is typically associated with the highest pathogenic grade and incidence in premenopausal and young African American (AA) women. Chemotherapy, the most common treatment for TNBC today, can lead to acquired resistance and ineffective treatment. Therefore, novel therapeutic approaches are needed to combat medication resistance and ineffectiveness in TNBC patients. Thymoquinone (TQ) is shown to have a cytotoxic effect on human cancer cells in vitro. However, TQ’s mode of action and precise mechanism in TNBC disease in vitro have not been adequately investigated. Therefore, TQ’s effects on the genetically different MDA-MB-468 and MDA-MB-231 human breast cancer cell lines were assessed. The data obtained show that TQ displayed cytotoxic effects on MDA-MB-468 and MDA-MB-231 cells in a time- and concentration-dependent manner after 24 h, with IC50 values of 25.37 µM and 27.39 µM, respectively. Moreover, MDA-MB-231 and MDA-MB-468 cells in a scratched wound-healing assay displayed poor wound closure, inhibiting invasion and migration via cell cycle blocking after 24 h. TQ arrested the cell cycle phase in MDA-MB-231 and MDA-MB-468 cells. The three cell cycle stages in MDA-MB-468 cells were significantly affected at 15 and 20 µM for G0/G1 and S phases, as well as all TQ concentrations for G2/M phases. In MDA-MB-468 cells, there was a significant decrease in G0/G1 phases with a substantial increase in the S phase and G2/M phases. In contrast, MDA-MB-231 showed a significant effect only during the two cell cycle stages (S and G2/M), at concentrations of 15 and 20 µM for S phases and all TQ values for G2/M phases. The TQ effect on the apoptotic gene profiles indicated that TQ upregulated 15 apoptotic genes in MDA-MB-231 TNBC cells, including caspases, GADD45A, TP53, DFFA, DIABLO, BNIP3, TRAF2/3, and TNFRSF10A. In MDA-MB-468 cells, 16 apoptotic genes were upregulated, including TNFRSF10A, TNF, TNFRSF11B, FADD TNFRSF10B, CASP2, and TRAF2, all of which are important for the apoptotic pathway andsuppress the expression of one anti-apoptotic gene, BIRC5, in MDA-MB-231 cells. Compared to MDA-MB-231 cells, elevated levels of TNF and their receptor proteins may contribute to their increased sensitivity to TQ-induced apoptosis. It was concluded from this study that TQ targets the MDA-MB-231 and MDA-MB-468 cells differently. Additionally, due to the aggressive nature of TNBC and the lack of specific therapies in chemoresistant TNBC, our findings related to the identified apoptotic gene profile may point to TQ as a potential agent for TNBC therapy.

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Section: Introductionmentioning

confidence: 99%

Thymoquinone Alterations of the Apoptotic Gene Expressions and Cell Cycle Arrest in Genetically Distinct Triple-Negative Breast Cancer Cells

et al. 2022

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“…Autophagy is a process found in low levels under normal conditions known as self-eating, which maintains cellular homeostasis balancing catabolic mechanisms. Autophagy is controlled by numerous pathways targeting multiple disease states, including viral and bacterial infections, cancer, diabetes, and neurodegenerative diseases [ 146 ]. It is activated in response to stress to remove excess damaging cellular proteins and organelles.…”

Section: Flavonoidsmentioning

confidence: 99%

“…It is activated in response to stress to remove excess damaging cellular proteins and organelles. Autophagy comprises five key steps: induction, nucleation, vesicle lengthening and maturation, vesicle fusion, and degradation and recycling [ 146 ]. These processes are regulated by the recruitment of autophagy-related protein repressed by the mechanistic target of rapamycin complex 1 [ 146 ].…”

Section: Flavonoidsmentioning

confidence: 99%

Neuroprotective Effects and Therapeutic Potential of the Citrus Flavonoid Hesperetin in Neurodegenerative Diseases

2022

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Neurodegenerative disorders affect more than fifty million Americans each year and represent serious health threats as the population ages. Neuroinflammation and oxidative stress are critical in the onset, progression, and pathogenesis of neurodegenerative diseases such as Alzheimer’s (AD), Parkinson’s (PD), and amyotrophic lateral sclerosis (ALS). A wide range of natural compounds has been investigated because of their antioxidant, anti-inflammatory, and neuroprotective properties. The citrus flavonoid hesperetin (HPT), an aglycone of hesperidin found in oranges, mandarins, and lemons, has been extensively reported to exert neuroprotective effects in experimental models of neurogenerative diseases. This review has compiled multiple studies on HPT in both in vivo and in vitro models to study neurodegeneration. We focused on the modulatory effects of hesperetin on the release of cellular anti-inflammatory and antioxidative stress mediators. Additionally, this review discusses the hesperetin effect in maintaining the levels of microRNA (miRNA) and modulating autophagy as it relates to hesperetin’s protective mechanisms against neurodegeneration. Moreover, this review is focused on providing experimental data for hesperetin’s potential as a neuroprotective compound and discusses reported evidence that HPT crosses the blood–brain barrier. In summary, this review shows the evidence available in the literature to indicate the efficacy of hesperetin in delaying the onset of neurodegenerative diseases.

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“…The ability of flavonoids to affect miRNAs involved in carcinogenesis (review, [ 135 , 136 ]) is particularly relevant in CSCs. Thus, in breast cancer cells, exposure to Glabridin, a phytochemical from the root of Glycyrrhiza glabra, upregulated miR-148a via promoter de-methylation, leading to the suppression of SMAD2 and decrease in CSC-like properties [ 137 ].…”

Section: Anti-csc Activity Of Flavonoids Mediated By Modulation Of Micrornasmentioning

confidence: 99%

Natural Products Targeting Cancer Stem Cells for Augmenting Cancer Therapeutics

Meerson

Khatib

Mahajna

2021

IJMS

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Cancer stem cells (CSC) have been identified in several types of solid tumors. In some cases, CSC may be the source of all the tumor cells, the cause of the tumor’s resistance to chemotherapeutic agents, and the source of metastatic cells. Thus, a combination therapy targeting non-CSC tumor cells as well as specifically targeting CSCs holds the potential to be highly effective. Natural products (NPs) have been a historically rich source of biologically active compounds and are known for their ability to influence multiple signaling pathways simultaneously with negligible side effects. In this review, we discuss the potential of NPs in targeting multiple signaling pathways in CSC and their potential to augment the efficacy of standard cancer therapy. Specifically, we focus on the anti-CSC activities of flavonoids, FDA-approved drugs originating from natural sources. Additionally, we emphasize the potential of NPs in targeting microRNA-mediated signaling, given the roles of microRNA in the maintenance of the CSC phenotype.

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The Anticancer Effects of Flavonoids through miRNAs Modulations in Triple-Negative Breast Cancer

Cited by 40 publications

References 353 publications

Thymoquinone Alterations of the Apoptotic Gene Expressions and Cell Cycle Arrest in Genetically Distinct Triple-Negative Breast Cancer Cells

Thymoquinone Alterations of the Apoptotic Gene Expressions and Cell Cycle Arrest in Genetically Distinct Triple-Negative Breast Cancer Cells

Neuroprotective Effects and Therapeutic Potential of the Citrus Flavonoid Hesperetin in Neurodegenerative Diseases

Natural Products Targeting Cancer Stem Cells for Augmenting Cancer Therapeutics

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