Hit Identification and Functional Validation of Novel Dual Inhibitors of HDAC8 and Tubulin Identified by Combining Docking and Molecular Dynamics Simulations DOI Creative Commons
Antonio Curcio, Roberta Rocca,

Federica Chiera

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(11), P. 1427 - 1427

Published: Nov. 20, 2024

Chromatin organization, which is under the control of histone deacetylases (HDACs), frequently deregulated in cancer cells. Amongst HDACs, HDAC8 plays an oncogenic role different neoplasias by acting on both and non-histone substrates. Promising anti-cancer strategies have exploited dual-targeting drugs that inhibit tubulin. These shown potential to enhance outcome treatments simultaneously targeting multiple pathways critical disease onset progression. In this study, a structure-based virtual screening (SBVS) 96403 natural compounds was performed towards four Class I HDAC isoforms Using molecular docking dynamics simulations (MDs), we identified two molecules could selectively interact with CNP0112925 (arundinin), bearing polyphenolic structure, confirmed activity tubulin affecting breast cell viability triggering mitochondrial superoxide production apoptosis.

Language: Английский

Tunneling nanotubes between bone marrow stromal cells support transmitophagy and resistance to apoptosis in myeloma DOI Creative Commons
Antonio Giovanni Solimando,

Francesco Di Palma,

Vanessa Desantis

et al.

Blood Cancer Journal, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 9, 2025

Language: Английский

Citations

0
BET inhibitors (BETi) influence oxidative phosphorylation metabolism by affecting mitochondrial dynamics leading to alterations in apoptotic pathways in triple‐negative breast cancer (TNBC) cells DOI Creative Commons
Teresa Rossi, Egidio Iorio, Mattea Chirico

et al.

Cell Proliferation, Journal Year: 2024, Volume and Issue: 57(12)

Published: Sept. 2, 2024

Repressing BET proteins' function using bromodomain inhibitors (BETi) has been shown to elicit antitumor effects by regulating the transcription of genes downstream BRD4. We previously showed that BETi promoted cell death triple-negative breast cancer (TNBC) cells. Here, we proved induce altered mitochondrial dynamics fitness in TNBC cells falling death. demonstrated treatment downregulated expression BCL-2, and proteins involved fission increased fused mitochondria. Impaired affected oxidative phosphorylation (OXPHOS) inducing OXPHOS-related genes, SDHa ATP5a, Consistently, amount DNA membrane potential (∆Ψm) BETi-treated compared control Lastly, combination with Metformin reduced growth. Our results indicate OXPHOS metabolism support proliferation represent novel targets

Language: Английский

Citations

2
A Review of Advances in Mitochondrial Research in Cancer DOI Creative Commons
Zhiru Li, Wu Zhang,

Shaowei Guo

et al.

Cancer Control, Journal Year: 2024, Volume and Issue: 31

Published: Jan. 1, 2024

Abnormalities in mitochondrial structure or function are closely related to the development of malignant tumors. Mitochondrial metabolic reprogramming provides precursor substances and energy for vital activities tumor cells, so that cancer cells can rapidly adapt unfavorable environment hypoxia nutrient deficiency. Mitochondria enable gain ability proliferate, escape immune responses, develop drug resistance by altering constitutive junctions, oxidative phosphorylation, stress, subcellular relocalization. This greatly reduces rate effective clinical control

Language: Английский

Citations

2
Hit Identification and Functional Validation of Novel Dual Inhibitors of HDAC8 and Tubulin Identified by Combining Docking and Molecular Dynamics Simulations DOI Creative Commons
Antonio Curcio, Roberta Rocca,

Federica Chiera

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(11), P. 1427 - 1427

Published: Nov. 20, 2024

Chromatin organization, which is under the control of histone deacetylases (HDACs), frequently deregulated in cancer cells. Amongst HDACs, HDAC8 plays an oncogenic role different neoplasias by acting on both and non-histone substrates. Promising anti-cancer strategies have exploited dual-targeting drugs that inhibit tubulin. These shown potential to enhance outcome treatments simultaneously targeting multiple pathways critical disease onset progression. In this study, a structure-based virtual screening (SBVS) 96403 natural compounds was performed towards four Class I HDAC isoforms Using molecular docking dynamics simulations (MDs), we identified two molecules could selectively interact with CNP0112925 (arundinin), bearing polyphenolic structure, confirmed activity tubulin affecting breast cell viability triggering mitochondrial superoxide production apoptosis.

Language: Английский

Citations

1