J 2024

Short-term autophagy inhibition by autophinib or SAR405 does not alter the effect of cisplatin on ATP production in prostate cancer cells

KRATOCHVÍLOVÁ, Monika, Petr ŠTĚPKA, Martina RAUDENSKÁ, Jan BALVAN, Lukáš RICHTERA et. al.

Základní údaje

Originální název

Short-term autophagy inhibition by autophinib or SAR405 does not alter the effect of cisplatin on ATP production in prostate cancer cells

Autoři

KRATOCHVÍLOVÁ, Monika (203 Česká republika, garant, domácí), Petr ŠTĚPKA (203 Česká republika, domácí), Martina RAUDENSKÁ (203 Česká republika, domácí), Jan BALVAN (203 Česká republika, domácí), Lukáš RICHTERA (203 Česká republika), Natalia CERNEI (203 Česká republika), Dagmar SKOPALOVA STERBOVA (203 Česká republika), Ondrej ZITKA (203 Česká republika), Petr FILIPENSKÝ (203 Česká republika), Petr BABULA (203 Česká republika, domácí) a Michal MASAŘÍK (203 Česká republika, domácí)

Vydání

Bratislava Medical Journal - Bratislavské lekárske listy, BRATISLAVA, Univerzita Komenského, 2024, 0006-9248

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Slovensko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 1.500 v roce 2022

Organizační jednotka

Lékařská fakulta

UT WoS

001202183600010

Klíčová slova anglicky

cisplatin; autophagy inhibition; amino acids; prostate cancer.

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 5. 6. 2024 13:07, Mgr. Tereza Miškechová

Anotace

V originále

OBJECTIVES: Cisplatin is a widely used anticancer drug for the treatment of many solid cancers. DNA damage is thought to be the key mechanism of cisplatin's anticancer activity. However, cisplatin may also affect cellular metabolism. The aim of this study was to determine the effect of cisplatin on the types of ATP production (OXPHOS versus glycolysis) and their rate in prostate cancer cells and to determine the potentially protective effect of autophagy and amino acids during cisplatin treatment. We also wanted to investigate the potential synergy between the metabolic effects of cisplatin on ATP production and the inhibition of autophagy. METHODS: We used two models of autophagy inhibition, a natural model of dysfunctional autophagy-DU145 cells and 24 -hour inhibition of autophagy by autophinib or SAR405. The effect of cisplatin and autophagy inhibition was observed on prostate cancer cell lines 22Rv1, PC -3, and DU145. To assess the type (OXPHOS versus glycolysis) and rate of ATP production, the Seahorse XF Real -Time ATP Rate Assay was performed by measuring the extracellular acidification rates (ECAR) as a proxy for glycolytic readouts and the oxygen consumption rates (OCR) as a proxy for oxidative phosphorylation readouts. We also performed quantitative phase imaging and colony -forming assay to assess the metastatic potential of cancer cells. Finally, amino acid profiles were examined using ion -exchange liquid chromatography. RESULTS: After cisplatin treatment, ATP production by OXPHOS was significantly decreased in 22Rv1 and PC -3 cells. On the other hand, ATP production by glycolysis was not significantly affected in 22Rv1 cells. DU145 cells with dysfunctional autophagy were the most sensitive to cisplatin treatment and showed the lowest ATP production. However, short-term autophagy inhibition (24h) by autophinib or SAR405 in 22Rv1 and PC -3 cells did not alter the effect of cisplatin on ATP production. Levels of some amino acids (arginine, methionine) significantly affected the fitness of cancer cells. CONCLUSION: Persistent defects of autophagy can affect the metabolic sensitivity of cancer cells due to interference with arginine metabolism. Amino acids contained in the culture medium had an impact on the overall effect of cisplatin (Fig. 3, Ref. 38). Text in PDF www.elis.sk