Self-Assembling Amphiphilic Peptides Target the VDAC1-Hexokinase-II Complex to Induce Apoptosis in Cervical Carcinoma Cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F10974938%3A_____%2F25%3A25_88_27" target="_blank" >RIV/10974938:_____/25:25_88_27 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1021/acs.jmedchem.4c02789" target="_blank" >https://doi.org/10.1021/acs.jmedchem.4c02789</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jmedchem.4c02789" target="_blank" >10.1021/acs.jmedchem.4c02789</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Self-Assembling Amphiphilic Peptides Target the VDAC1-Hexokinase-II Complex to Induce Apoptosis in Cervical Carcinoma Cells

Popis výsledku v původním jazyce

VDAC1, an outer mitochondrial membrane protein overexpressed in cancers, regulates apoptosis by interacting with antiapoptotic proteins and releasing apoptotic factors. We investigate novel multiblock cationic peptide amphiphiles targeting the VDAC1-Hexokinase-II complex in the mitochondria of cervical carcinoma cells. Amphiphilic peptide variants were designed by modifying the C-terminus of VDAC1 fragment LP1 with a cationic hydrophilic segment and the N-terminus with a hydrophobic domain, enabling self-assembly into nanofiber-like structures at elevated concentrations. In HeLa cells, these peptides triggered mitochondrial-mediated apoptosis through a decrease of the mitochondrial membrane potential, cytochrome C release, and caspase activation, suggesting a disrupted VDAC1-HK-II interaction. The mitochondria-targeting peptides showed notable selective cytotoxicity to cancer cells, with minimal effects on normal 3T3 cells. Our findings demonstrate that amphiphilic peptides for VDAC1-HK-II-targeting represent a promising mitochondria-focused therapeutic strategy for cervical cancer inhibition, combining structural self-assembly properties with enhanced apoptotic efficacy in malignant cells.

Název v anglickém jazyce

Self-Assembling Amphiphilic Peptides Target the VDAC1-Hexokinase-II Complex to Induce Apoptosis in Cervical Carcinoma Cells

Popis výsledku anglicky

VDAC1, an outer mitochondrial membrane protein overexpressed in cancers, regulates apoptosis by interacting with antiapoptotic proteins and releasing apoptotic factors. We investigate novel multiblock cationic peptide amphiphiles targeting the VDAC1-Hexokinase-II complex in the mitochondria of cervical carcinoma cells. Amphiphilic peptide variants were designed by modifying the C-terminus of VDAC1 fragment LP1 with a cationic hydrophilic segment and the N-terminus with a hydrophobic domain, enabling self-assembly into nanofiber-like structures at elevated concentrations. In HeLa cells, these peptides triggered mitochondrial-mediated apoptosis through a decrease of the mitochondrial membrane potential, cytochrome C release, and caspase activation, suggesting a disrupted VDAC1-HK-II interaction. The mitochondria-targeting peptides showed notable selective cytotoxicity to cancer cells, with minimal effects on normal 3T3 cells. Our findings demonstrate that amphiphilic peptides for VDAC1-HK-II-targeting represent a promising mitochondria-focused therapeutic strategy for cervical cancer inhibition, combining structural self-assembly properties with enhanced apoptotic efficacy in malignant cells.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10301 - Atomic, molecular and chemical physics (physics of atoms and molecules including collision, interaction with radiation, magnetic resonances, Mössbauer effect)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Medicinal Chemistry

ISSN

0022-2623

e-ISSN

1520-4804

Svazek periodika

68

Číslo periodika v rámci svazku

18

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

18857-18868

Kód UT WoS článku

001570866200001

EID výsledku v databázi Scopus

2-s2.0-105017023524