Suppression of autophagy enhances preferential toxicity of epothilone A and epothilone B in ovarian cancer cells

Rogalska, Aneta; Gajek, Arkadiusz; Marczak, Agnieszka

doi:10.1016/j.phymed.2019.152847

Cited by 13 publications

(12 citation statements)

References 29 publications

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“…Finally, four potential sensitive drugs, including staurosporine, epothilone B, DMOG, and HG6-64-1, were screened out (Figures 6(c)-6(e)). It has been previously reported that staurosporine [37], epothilone B [38,39], and HG6-64-1 have a therapeutic effect on ovarian cancer [40]. Critically, we identified that a novel potential sensitive drug is dimethyloxallyl glycine (DMOG), a kind of prolyl hydroxylase inhibitor (PHI), may be able to treat invasive ovarian cancer.…”

Section: Identification Of Potential Targeted Drugs To High-scorementioning

confidence: 99%

Ferroptosis-Related Gene Signature Promotes Ovarian Cancer by Influencing Immune Infiltration and Invasion

Yang

Huang

et al. 2021

Journal of Oncology

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Ovarian cancer is a kind of gynecological malignancy with high mortality. Ferroptosis is a new type of iron-dependent cell death characterized by the formation of lipid peroxides and excessive accumulation of reactive oxygen species. Studies have shown that ferroptosis modulates tumor genesis, progression, and invasion, including ovarian cancer. Based on the mRNA expression data from TCGA, we construct a scoring system using consensus clustering analysis, univariate Cox regression analysis, and least absolute selection operator. Then, we systematically evaluate the relationship between score and clinical characteristics of ovarian cancer. The result from the prediction of biofunction pathways shows that score serves as an independent prognostic marker for ovarian cancer and affects tumor progression by modulating tumor metastasis. Moreover, immunocytes such as activated CD4 T cell, activated CD8 T cell, regulatory T cells, macrophage, and stromal cells, including adipocytes, epithelial cells, and fibroblast infiltrate more in the tumor microenvironment in a high-score group, indicating ferroptosis can also affect tumor immune landscape. Critically, four potentially sensitive drugs, including staurosporine, epothilone B, DMOG, and HG6-64-1 based on the scores, are predicted, and DMOG is recognized as a novel targeted drug for ovarian cancer. In general, we construct the scoring system based on ferroptosis-related genes that can predict the prognosis of ovarian cancer patients and propose that ferroptosis may affect ovarian cancer progression by mediating tumor metastasis and immune landscape. Novel drugs to target ovarian cancer are also predicted.

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Section: Identification Of Potential Targeted Drugs To High-scorementioning

confidence: 99%

Ferroptosis-Related Gene Signature Promotes Ovarian Cancer by Influencing Immune Infiltration and Invasion

Yang

Huang

et al. 2021

Journal of Oncology

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“…As a result, the synthesis of optically pure alcohols has attracted significant interest from academia and industry due to their broad applications. [1,2] This is exemplified by the presence of chiral alcohols as structural elements in numerous pharmaceutically active compounds (Figure 1), such as Isoprenaline (βadrenoreceptor agonist), [3] Duloxetine (anti-depressant), [4] and Epothilone A [5] (anti-tumor), as well as in agrochemicals, fragrances and other biologically active molecules. A common way to obtain enantioenriched alcohols is by the asymmetric reduction of ketones.…”

Section: Introductionmentioning

confidence: 99%

Chemo‐ and Enantioselective Photoenzymatic Ketone Reductions Using a Promiscuous Flavin‐dependent Nitroreductase

et al. 2022

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Flavoenzymes are oxidoreductases that catalyze an extensive range of different types of reactions.An advanced and powerful approach to achieving transformations that are normally outside the realm of flavoenzymes is the synergistic combination of photocatalysis and biocatalysis. Here we report the identification of a promiscuous flavin-dependent nitroreductase, BaNTR1, that is able to promote enantioselective photobiocatalytic reductions of a broad range of structurally diverse ketones to yield the corresponding alcohols with high conversion (up to >99%) and outstanding enantiopurity (up to >99:1 e.r). Noteworthy, BaNTR1 was able to promote the photoenzymatic reduction of various α,ßunsaturated ketones to give the corresponding optically pure alcohols without reducing the C=C or C≡C bond, illustrating its remarkably high chemoselectivity. Our results highlight the usefulness of photocatalysis for expanding the catalytic repertoire of nitroreductases to include highly enantio-and chemoselective reductions of non-native ketone substrates to produce optically pure alcohols. This includes difficult to prepare allyl alcohols that are not accessible via photoenzymatic conversions using ene-reductases.

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“…The activity of caspase-3 and -7 was estimated with the Apo-ONE ® Homogeneous Caspase 3/7 Assay (Promega Corporation, Madison, WI, USA) according to the manufacturer’s protocols, as described in our previous article [ 93 ]. Measurement of caspase activation in the control and treated cells seeded in 96 black well plates was recorded by monitoring changes in fluorescence after 24 h of incubation with the investigated compounds.…”

Section: Methodsmentioning

confidence: 99%

Metformin Affects Olaparib Sensitivity through Induction of Apoptosis in Epithelial Ovarian Cancer Cell Lines

Gralewska

Gajek

Marczak

et al. 2021

IJMS

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This study examined the effect of combination treatment with the poly (ADP-ribose) polymerase inhibitor olaparib and metformin on homologous recombination (HR)-proficient epithelial ovarian cancer (EOC). Ovarian cancer cell lines (OV-90 and SKOV-3) were treated with olaparib, metformin, or a combination of both. Cell viability was assessed by MTT and colony formation assays. The production of reactive oxygen species (ROS) and changes in mitochondrial membrane potential were examined using the specific fluorescence probes, DCFH2-DA (2′,7′-dichloro-dihydrofluorescein diacetate) and JC-1 (5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine). Apoptotic and necrotic changes were measured by double staining with Hoechst 33258 and propidium iodide, orange acridine and ethidium bromide staining, phosphatidylserine externalization, TUNEL assay, caspase 3/7 activity, and cytochrome c and p53 expression. Compared with single-drug treatment, the combination of olaparib and metformin significantly inhibited cell proliferation and colony formation in HR-proficient ovarian cancer cells. ROS production preceded a decrease in mitochondrial membrane potential. The changes in ROS levels suggested their involvement in inducing apoptosis in response to combination treatment. The present results indicate a shift towards synergism in cells with mutant or null p53, treated with olaparib combined with metformin, providing a new approach to the treatment of gynecologic cancers. Taken together, the results support the use of metformin to sensitize EOC to olaparib therapy.

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Suppression of autophagy enhances preferential toxicity of epothilone A and epothilone B in ovarian cancer cells

Cited by 13 publications

References 29 publications

Ferroptosis-Related Gene Signature Promotes Ovarian Cancer by Influencing Immune Infiltration and Invasion

Ferroptosis-Related Gene Signature Promotes Ovarian Cancer by Influencing Immune Infiltration and Invasion

Chemo‐ and Enantioselective Photoenzymatic Ketone Reductions Using a Promiscuous Flavin‐dependent Nitroreductase

Metformin Affects Olaparib Sensitivity through Induction of Apoptosis in Epithelial Ovarian Cancer Cell Lines

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