Biotinylation enhances the anticancer effects of 15d‑PGJ2 against breast cancer cells

Colin, Christelle; Meyer, Maxime; Cerella, Claudia; Kleinclauss, Alexandra; Monard, Gérald; Boisbrun, Michel; Diederich, Marc; Flament, Stï¿1⁄2phane; Grillier-Vuissoz, Isabelle; Kuntz, Sandra

doi:10.3892/ijo.2018.4338

Cited by 6 publications

(4 citation statements)

References 59 publications

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“…Here, we studied two TGZ derivatives, Δ2-TGZ and AB186, that we have previously shown to inhibit cell growth and to induce breast cancer cell death [ 14 , 20 ]. Interestingly, AB186 is a more potent inhibitor of TNBC cell proliferation than efatutazone, a TZD used in combination with chemotherapy drug to treat cancer [ 14 , 25 ]. Our aim was to better understand the mechanism of action of these two derivatives.…”

Section: Discussionmentioning

confidence: 99%

AB186 Inhibits Migration of Triple-Negative Breast Cancer Cells and Interacts with α-Tubulin

Geoffroy

Lemesle

Kleinclauss

et al. 2022

IJMS

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Breast cancer is one of the leading causes of cancer-related death among females worldwide. A major challenge is to develop innovative therapy in order to treat breast cancer subtypes resistant to current treatment. In the present study, we examined the effects of two Troglitazone derivatives Δ2-TGZ and AB186. Previous studies showed that both compounds induce apoptosis, nevertheless AB186 was a more potent agent. The kinetic of cellular events was investigated by real-time cell analysis system (RTCA) in MCF-7 (hormone dependent) and MDA-MB-231 (triple negative) breast cancer (TNBC) cells, followed by cell morphology analysis by immuno-localization. Both compounds induced a rapid modification of both impedance-based signals and cellular morphology. This process was associated with an inhibition of cell migration measured by wound healing and transwell assays in TNBC MDA-MB-231 and Hs578T cells. In order to identify cytoplasmic targets of AB186, we performed surface plasmon resonance (SPR) and pull-down analyses. Subsequently, 6 cytoskeleton components were identified as potential targets. We further validated α-tubulin as one of the direct targets of AB186. In conclusion, our results suggested that AB186 could be promising to develop novel therapeutic strategies to treat aggressive forms of breast cancer such as TNBC.

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Section: Discussionmentioning

confidence: 99%

AB186 Inhibits Migration of Triple-Negative Breast Cancer Cells and Interacts with α-Tubulin

Geoffroy

Lemesle

Kleinclauss

et al. 2022

IJMS

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“…Moreover, our metabolomics ndings revealed an increase in speci city of histamine, 15-deoxy-Δ12,14prostaglandin J2 (15-PGJ2), and aliphatic acyclic compounds. Several studies have con rmed that 15-PGJ2 had signi cant anticancer effects [19][20][21] . It also has anti-in ammatory, antiangiogenic, and proapoptotic properties.…”

Section: Discussionmentioning

confidence: 99%

Multi-omics Research on the Heterogeneity and Immune Landscape of Lung Adenocarcinoma with Ground-glass opacity

Miao

Teng

et al. 2022

Preprint

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Background: Lung adenocarcinoma with ground-glass opacity (GGO) has been detected increasingly and now accounts for most lung cancer patients. Lung adenocarcinoma with GGO contains a complex ecosystem. The mechanism of lung adenocarcinoma with GGO remains largely elusive. We use mass spectrometry proteomics combined with metabolomics to understand how these characteristics achieve a long-term functional balance and the trend of changes in tumor progression at the cellular functional level. Methods: We initiated a prospective cohort study to characterize lung adenocarcinoma with GGO components or without GGO components. Tumor and para-cancer tissue samples were collected. Multi-omics including transcriptomics proteomics and metabonomics were performed. Results: We found lung adenocarcinoma with GGO had a relatively slow proliferation tumor cells and stronger immune cell infiltration in proteomic and transcriptomic analysis. The immune cell markers expression, including CD47, CD68, CD81, CD86, C1Q, SPP1, CXCL13, ALOX5AP and HPGD was found overexpression in lung adenocarcinoma with GGO, which indicated more immune cell infiltration. In metabolomic analysis, GAPDH, ENO1 and LDHA were highly expressed in pure-solid lung adenocarcinoma, and GPD1 was highly expressed in lung adenocarcinoma with GGO. The combined transcriptome and proteome analysis revealed that proteins with consistent differences mainly included GAPDH, MKI67, AGER, and CRYM. KEGG pathway enrichment analysis showed that several aliphatic acyclic compounds expression were higher in lung adenocarcinoma with GGO. Conclusion: We describe a functional homeostasis in lung adenocarcinoma with GGO, which was constructed by relatively slow proliferation tumor cells and stronger immune cell infiltration. Overexpression of CXCL13 drives the infiltration of immune cells, which means the formation of anti-tumor tertiary lymphatic structures. The dysfunction of macrophage may be an important marker of this progression.

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“…Interestingly, AB186 is a more potent inhibitor of TNBC cell proliferation than efatutazone, a TZD used in combination with chemotherapy drug to treat cancer [14,26]. Our aim was to better understand the mechanism of action of these two derivatives.…”

Section: Discussionmentioning

confidence: 99%

Troglitazone Derivatives Induce Early Modifications of the Cytoskeleton and Inhibition of Migration in Breast Cancer Cells

Geoffroy

Lemesle

Kleinclauss

et al. 2021

Preprint

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Background The 5-years survival rate of breast cancer patients is around 90%. Unfortunately, some types of tumors, especially the triple negative breast cancer (TNBC), present chemo-resistance and have a higher relapse 5 years post-treatment due to metastasis. These challenges highlight the need for the development of new drugs for these tumors. In this context, we developed new troglitazone derivatives as support for such potential new treatment.Methods The kinetic of early cellular events was investigated after Δ2-TGZ and AB186 treatment by real-time cell analysis system (RTCA) in MCF-7 and MDA-MB-231 breast cancer cells, followed by cell morphology analysis by immuno-localization. Then, we characterized the action of both compounds on the cell migration by wound healing and transwell assays in TNBC MDA-MB-231 and Hs578T cell lines. Finally, we performed surface plasmon resonance (SPR) analysis and pull-down assay using biotinylated AB186 to identify cytoplasmic targets.Results Δ2-TGZ and AB186 induced a rapid modification of impedance-based signals and morphology in MCF7 and MDA-MB-231 breast cancer cell lines. This process was associated with an inhibition of cell migration in MDA-MB-231 and Hs578T cell lines. Subsequently, 6 cytoskeleton components have been identified as potential targets of AB186 in MDA-MB-231 cytoplasmic fraction. We further validated α-tubulin as one of the direct targets of AB186.Conclusion New troglitazone derivatives, Δ2-TGZ and AB186, induced early cell morphological changes and showed anti-migratory effects on TNBC cells suggesting that these drugs could be proposed as novel candidates to treat TNBC patients.

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Biotinylation enhances the anticancer effects of 15d‑PGJ2 against breast cancer cells

Cited by 6 publications

References 59 publications

AB186 Inhibits Migration of Triple-Negative Breast Cancer Cells and Interacts with α-Tubulin

AB186 Inhibits Migration of Triple-Negative Breast Cancer Cells and Interacts with α-Tubulin

Multi-omics Research on the Heterogeneity and Immune Landscape of Lung Adenocarcinoma with Ground-glass opacity

Troglitazone Derivatives Induce Early Modifications of the Cytoskeleton and Inhibition of Migration in Breast Cancer Cells

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