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

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.

Basic information

Original name

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

Authors

KRATOCHVÍLOVÁ, Monika (203 Czech Republic, guarantor, belonging to the institution), Petr ŠTĚPKA (203 Czech Republic, belonging to the institution), Martina RAUDENSKÁ (203 Czech Republic, belonging to the institution), Jan BALVAN (203 Czech Republic, belonging to the institution), Lukáš RICHTERA (203 Czech Republic), Natalia CERNEI (203 Czech Republic), Dagmar SKOPALOVA STERBOVA (203 Czech Republic), Ondrej ZITKA (203 Czech Republic), Petr FILIPENSKÝ (203 Czech Republic), Petr BABULA (203 Czech Republic, belonging to the institution) and Michal MASAŘÍK (203 Czech Republic, belonging to the institution)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Slovakia

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 1.500 in 2022

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.4149/BLL_2024_013

UT WoS

001202183600010

Keywords in English

cisplatin; autophagy inhibition; amino acids; prostate cancer.

Abstract

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

Citovat

KRATOCHVÍLOVÁ, Monika, Petr ŠTĚPKA, Martina RAUDENSKÁ, Jan BALVAN, Lukáš RICHTERA, Natalia CERNEI, Dagmar SKOPALOVA STERBOVA, Ondrej ZITKA, Petr FILIPENSKÝ, Petr BABULA and Michal MASAŘÍK. Short-term autophagy inhibition by autophinib or SAR405 does not alter the effect of cisplatin on ATP production in prostate cancer cells. Bratislava Medical Journal - Bratislavské lekárske listy. BRATISLAVA: Univerzita Komenského, 2024, vol. 125, No 2, p. 84-91. ISSN 0006-9248. Available from: https://dx.doi.org/10.4149/BLL_2024_013.

@article{2407958,
   author = {Kratochvílová, Monika and Štěpka, Petr and Raudenská, Martina and Balvan, Jan and Richtera, Lukáš and Cernei, Natalia and Skopalova Sterbova, Dagmar and Zitka, Ondrej and Filipenský, Petr and Babula, Petr and Masařík, Michal},
   article_location = {BRATISLAVA},
   article_number = {2},
   doi = {http://dx.doi.org/10.4149/BLL_2024_013},
   keywords = {cisplatin; autophagy inhibition; amino acids; prostate cancer.},
   language = {eng},
   issn = {0006-9248},
   journal = {Bratislava Medical Journal - Bratislavské lekárske listy},
   title = {Short-term autophagy inhibition by autophinib or SAR405 does not alter the effect of cisplatin on ATP production in prostate cancer cells},
   url = {https://www.elis.sk/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=8175&category_id=194&option=com_virtuemart&vmcchk=1&Itemid=1},
   volume = {125},
   year = {2024}
}

TY  - JOUR
ID  - 2407958
AU  - Kratochvílová, Monika - Štěpka, Petr - Raudenská, Martina - Balvan, Jan - Richtera, Lukáš - Cernei, Natalia - Skopalova Sterbova, Dagmar - Zitka, Ondrej - Filipenský, Petr - Babula, Petr - Masařík, Michal
PY  - 2024
TI  - Short-term autophagy inhibition by autophinib or SAR405 does not alter the effect of cisplatin on ATP production in prostate cancer cells
JF  - Bratislava Medical Journal - Bratislavské lekárske listy
VL  - 125
IS  - 2
SP  - 84-91
EP  - 84-91
PB  - Univerzita Komenského
SN  - 00069248
KW  - cisplatin
KW  - autophagy inhibition
KW  - amino acids
KW  - prostate cancer.
UR  - https://www.elis.sk/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=8175&category_id=194&option=com_virtuemart&vmcchk=1&Itemid=1
N2  - 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
ER  -

KRATOCHVÍLOVÁ, Monika, Petr ŠTĚPKA, Martina RAUDENSKÁ, Jan BALVAN, Lukáš RICHTERA, Natalia CERNEI, Dagmar SKOPALOVA STERBOVA, Ondrej ZITKA, Petr FILIPENSKÝ, Petr BABULA and Michal MASAŘÍK. Short-term autophagy inhibition by autophinib or SAR405 does not alter the effect of cisplatin on ATP production in prostate cancer cells. \textit{Bratislava Medical Journal - Bratislavské lekárske listy}. BRATISLAVA: Univerzita Komenského, 2024, vol.~125, No~2, p.~84-91. ISSN~0006-9248. Available from: https://dx.doi.org/10.4149/BLL\_{}2024\_{}013.

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