Synergistic cytotoxicity of perifosine and ABT-737 to colon
cancer cells

J 2023

Synergistic cytotoxicity of perifosine and ABT-737 to colon cancer cells

ADAMOVÁ, Barbora; Kamila ŘÍHOVÁ; Jana POKLUDOVÁ; Petr BENEŠ; Jan ŠMARDA et al.

Základní údaje

Originální název

Synergistic cytotoxicity of perifosine and ABT-737 to colon cancer cells

Autoři

ADAMOVÁ, Barbora; Kamila ŘÍHOVÁ ; Jana POKLUDOVÁ; Petr BENEŠ; Jan ŠMARDA a Jarmila NAVRÁTILOVÁ

Vydání

Journal of Cellular and Molecular Medicine, Wiley, 2023, 1582-1838

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.300

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/23:00130107

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

ABT-737; colon cancer; combined treatment; peeling analysis; perifosine; spheroids; synergism; tumour microenvironment

Štítky

14314010, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 27. 2. 2024 08:38, Mgr. Jarmila Navrátilová, Ph.D.

Anotace

V originále

An acidic environment and hypoxia within the tumour are hallmarks of cancer that contribute to cell resistance to therapy. Deregulation of the PI3K/Akt pathway is common in colon cancer. Numerous Akt-targeted therapies are being developed, the activity of Akt-inhibitors is, however, strongly pH-dependent. Combination therapy thus represents an opportunity to increase their efficacy. In this study, the cytotoxicity of the Akt inhibitor perifosine and the Bcl-2/Bcl-xL inhibitor ABT-737 was tested in colon cancer HT-29 and HCT-116 cells cultured in monolayer or in the form of spheroids. The efficacy of single drugs and their combination was analysed in different tumour-specific environments including acidosis and hypoxia using a series of viability assays. Changes in protein content and distribution were determined by immunoblotting and a “peeling analysis” of immunohistochemical signals. While the cytotoxicity of single agents was influenced by the tumour-specific microenvironment, perifosine and ABT-737 in combination synergistically induced apoptosis in cells cultured in both 2D and 3D independently on pH and oxygen level. Thus, the combined therapy of perifosine and ABT-737 could be considered as a potential treatment strategy for colon cancer.

Návaznosti

LX22NPO5102, projekt VaV

Název: Národní ústav pro výzkum rakoviny (Akronym: NÚVR)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní ústav pro výzkum rakoviny, 5.1 EXCELES

Přiložené soubory

Citovat

ADAMOVÁ, Barbora; Kamila ŘÍHOVÁ; Jana POKLUDOVÁ; Petr BENEŠ; Jan ŠMARDA a Jarmila NAVRÁTILOVÁ. Synergistic cytotoxicity of perifosine and ABT-737 to colon cancer cells. Journal of Cellular and Molecular Medicine. Wiley, 2023, roč. 27, č. 1, s. 76-88. ISSN 1582-1838. Dostupné z: https://doi.org/10.1111/jcmm.17636.

@article{2240071,
   author = {Adamová, Barbora and Říhová, Kamila and Pokludová, Jana and Beneš, Petr and Šmarda, Jan and Navrátilová, Jarmila},
   article_number = {1},
   doi = {https://doi.org/10.1111/jcmm.17636},
   keywords = {ABT-737; colon cancer; combined treatment; peeling analysis; perifosine; spheroids; synergism; tumour microenvironment},
   language = {eng},
   issn = {1582-1838},
   journal = {Journal of Cellular and Molecular Medicine},
   title = {Synergistic cytotoxicity of perifosine and ABT-737 to colon cancer cells},
   url = {https://onlinelibrary.wiley.com/doi/10.1111/jcmm.17636},
   volume = {27},
   year = {2023}
}

TY  - JOUR
ID  - 2240071
AU  - Adamová, Barbora - Říhová, Kamila - Pokludová, Jana - Beneš, Petr - Šmarda, Jan - Navrátilová, Jarmila
PY  - 2023
TI  - Synergistic cytotoxicity of perifosine and ABT-737 to colon cancer cells
JF  - Journal of Cellular and Molecular Medicine
VL  - 27
IS  - 1
SP  - 76-88
EP  - 76-88
PB  - Wiley
SN  - 15821838
KW  - ABT-737
KW  - colon cancer
KW  - combined treatment
KW  - peeling analysis
KW  - perifosine
KW  - spheroids
KW  - synergism
KW  - tumour microenvironment
UR  - https://onlinelibrary.wiley.com/doi/10.1111/jcmm.17636
N2  - An acidic environment and hypoxia within the tumour are hallmarks of cancer that contribute to cell resistance to therapy. Deregulation of the PI3K/Akt pathway is common in colon cancer. Numerous Akt-targeted therapies are being developed, the activity of Akt-inhibitors is, however, strongly pH-dependent. Combination therapy thus represents an opportunity to increase their efficacy. In this study, the cytotoxicity of the Akt inhibitor perifosine and the Bcl-2/Bcl-xL inhibitor ABT-737 was tested in colon cancer HT-29 and HCT-116 cells cultured in monolayer or in the form of spheroids. The efficacy of single drugs and their combination was analysed in different tumour-specific environments including acidosis and hypoxia using a series of viability assays. Changes in protein content and distribution were determined by immunoblotting and a “peeling analysis” of immunohistochemical signals. While the cytotoxicity of single agents was influenced by the tumour-specific microenvironment, perifosine and ABT-737 in combination synergistically induced apoptosis in cells cultured in both 2D and 3D independently on pH and oxygen level. Thus, the combined therapy of perifosine and ABT-737 could be considered as a potential treatment strategy for colon cancer.
ER  -

ADAMOVÁ, Barbora; Kamila ŘÍHOVÁ; Jana POKLUDOVÁ; Petr BENEŠ; Jan ŠMARDA a Jarmila NAVRÁTILOVÁ. Synergistic cytotoxicity of perifosine and ABT-737 to colon cancer cells. \textit{Journal of Cellular and Molecular Medicine}. Wiley, 2023, roč.~27, č.~1, s.~76-88. ISSN~1582-1838. Dostupné z: https://doi.org/10.1111/jcmm.17636.

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