Icariin induces apoptosis by suppressing autophagy in tamoxifen-resistant breast cancer cell line MCF-7/TAM

Cheng, Xiao; Tan, Shirui; Duan, Feifei; Yuan, Quan; Li, Qingrong; Deng, Gang

doi:10.1007/s12282-019-00980-5

Cited by 45 publications

(31 citation statements)

References 49 publications

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“…Resveratrol improves the sensitivity of BC chemotherapy and prevents the development of cancer by targeting miR-122-5, and then influences the expression of CDK2, CDK4, and CDK6, resulting in cell-cycle arrest [162]. Icariin, the main component with antitumor activity extracted from Epimedium brevicornum Maxim, decreases the expression of CDK2 and CDK4 to cause cell-cycle arrest in tamoxifen-resistant BC cell line MCF-7/TAM [163]. Tyrosine kinase WEE1 inhibitor AZD 1775 shows strong anti-proliferative effects.…”

Section: The Novel Cdk Inhibitors In Bcmentioning

confidence: 99%

The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer

Ding

Cao

Lin

et al. 2020

IJMS

382

216

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Cyclin-dependent kinases (CDKs) are serine/threonine kinases whose catalytic activities are regulated by interactions with cyclins and CDK inhibitors (CKIs). CDKs are key regulatory enzymes involved in cell proliferation through regulating cell-cycle checkpoints and transcriptional events in response to extracellular and intracellular signals. Not surprisingly, the dysregulation of CDKs is a hallmark of cancers, and inhibition of specific members is considered an attractive target in cancer therapy. In breast cancer (BC), dual CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, combined with other agents, were approved by the Food and Drug Administration (FDA) recently for the treatment of hormone receptor positive (HR+) advanced or metastatic breast cancer (A/MBC), as well as other sub-types of breast cancer. Furthermore, ongoing studies identified more selective CDK inhibitors as promising clinical targets. In this review, we focus on the roles of CDKs in driving cell-cycle progression, cell-cycle checkpoints, and transcriptional regulation, a highlight of dysregulated CDK activation in BC. We also discuss the most relevant CDK inhibitors currently in clinical BC trials, with special emphasis on CDK4/6 inhibitors used for the treatment of estrogen receptor-positive (ER+)/human epidermal growth factor 2-negative (HER2−) M/ABC patients, as well as more emerging precise therapeutic strategies, such as combination therapies and microRNA (miRNA) therapy.

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Section: The Novel Cdk Inhibitors In Bcmentioning

confidence: 99%

The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer

Ding

Cao

Lin

et al. 2020

IJMS

382

216

View full text Add to dashboard Cite

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“…Beclin 1 has been identified as a mammalian protein associated with autophagy and involved in cancer processes such as tumor suppression and cell death (48). Cheng et al (49) identified the role of autophagy in MCF-7 cells treated with Icariin (a flavonoid isolated from plants) by measuring the expression levels of ATG5, Beclin 1 and LC3-I to LC3-II proteins. Liang et al (50) demonstrated that exogenous Beclin 1 expression in MCF-7 cells resulted in decreased cell division and inhibition of tumorigenesis in a mouse model.…”

Section: Discussionmentioning

confidence: 99%

Mechanistic studies of cytotoxic activity of the mesoionic compound MIH 2.4Bl in MCF‑7 breast cancer cells

et al. 2020

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In the present study, the cytotoxic effects of a 1,3-thiazolium-5-thiolate derivative of a mesoionic compound, MIH 2.4Bl, were assessed in the MCF-7 breast cancer cell line. The cytotoxic effects of MIH 2.4Bl were determined using a crystal violet assay. Using a dose-response curve, the IC 50 value of MIH 2.4Bl was determined to be 45.8±0.8 µM. Additionally, the effects of MIH 2.4Bl on mitochondrial respiration were characterized using oxygen consumption rate analysis. Treating MCF-7 cells with increasing concentrations of MIH 2.4Bl resulted in a significant reduction in all mitochondrial respiratory parameters compared with the control cells, indicative of an overall decrease in mitochondrial membrane potential. The induction of autophagy by MIH 2.4Bl was also examined by measuring changes in the expression of protein markers of autophagy. As shown by western blot analysis, treatment of MCF-7 cells with MIH 2.4Bl resulted in increased protein expression levels of Beclin-1 and ATG5, as well as an increase in the microtubule-associated protein 1A/1B light chain 3B (LC3B)-II to LC3B-I ratio compared with the control cells. Microarray analysis of changes in gene expression following MIH 2.4Bl treatment demonstrated 3,659 genes exhibited a fold-change ≥2. Among these genes, 779 were up-regulated, and 2,880 were down-regulated in cells treated with MIH 2.4Bl compared with the control cells. Based on the identity of the transcripts and fold-change of expression, six genes were selected for verification by reverse transcription-quantitative (RT-q)PCR; activating transcription factor 3, acidic repeat-containing protein, heparin-binding EGF-like growth factor, regulator of G-protein signaling 2, Dickkopf WNT signaling pathway inhibitor 1 and adhesion molecule with Ig like domain 2. The results of RT-qPCR analysis of RNA isolated from control and MIH 2.4Bl treated cells were consistent with the expression changes identified by microarray analysis. Together, these results suggest that MIH 2.4Bl may be a promising candidate for treating breast cancer and warrants further in vitro and in vivo investigation.

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“…Additionally, studies have found that treatment of T-cell malignancies is accompanied with autophagy regulation 21 – 24 . Emerging reports have indicated that some flavonoids promote cell death by mediating autophagy in tumor cells 25 – 27 , such as wogonin 28 – 30 . FV-429, a derivative of wogonin, has been proved to exert anti-cancer effects in several solid tumors 31 – 33 .…”

Section: Introductionmentioning

confidence: 99%

FV-429 induces autophagy blockage and lysosome-dependent cell death of T-cell malignancies via lysosomal dysregulation

Wang

Qing

et al. 2021

Cell Death Dis

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It is widely accepted that lysosomes are essential for cell homeostasis, and autophagy plays an important role in tumor development. Here, we found FV-429, a synthetic flavonoid compound, inhibited autophagy flux, promoted autophagosomes accumulation, and inhibited lysosomal degradation in T-cell malignancies. These effects were likely to be achieved by lysosomal dysregulation. The destructive effects of FV-429 on lysosomes resulted in blockage of lysosome-associated membrane fusion, lysosomal membrane permeabilization (LMP), and cathepsin-mediated caspase-independent cell death (CICD). Moreover, we initially investigated the effects of autophagy inhibition by FV-429 on the therapeutic efficacy of chemotherapy and found that FV-429 sensitized cancer cells to chemotherapy agents. Our findings suggest that FV-429 could be a potential novel autophagy inhibitor with notable antitumor efficacy as a single agent.

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Icariin induces apoptosis by suppressing autophagy in tamoxifen-resistant breast cancer cell line MCF-7/TAM

Cited by 45 publications

References 49 publications

The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer

The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer

Mechanistic studies of cytotoxic activity of the mesoionic compound MIH 2.4Bl in MCF‑7 breast cancer cells

FV-429 induces autophagy blockage and lysosome-dependent cell death of T-cell malignancies via lysosomal dysregulation

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