The Assessment of the Effect of Autophagy Inhibitors—Chloroquine and 3-Methyladenine on the Antitumor Activity of Trametinib Against Amelanotic Melanoma Cells DOI Creative Commons
Dominika Stencel, Justyna Kowalska, Zuzanna Rzepka

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(7), P. 557 - 557

Published: April 7, 2025

Malignant melanoma, particularly amelanotic contributes to a very serious problem in public health. One way find new therapies is learn about and understand the molecular pathways that regulate cancer growth development. In case of tumor, autophagy process can lead development or inhibition cancer. This study aimed assess cytotoxicity connection trametinib (MEK1 MEK2 kinase inhibitor) with inhibitors—chloroquine (lysosomal clearance autophagosomes 3-methyladenine (phosphatidylinositol 3-kinases inhibitor), on two melanoma cell lines (C32 A-375). The results showed combination therapy had better anti-proliferative effects than alone both lines. C32 line was more sensitive treatment (alone combinations), A375 sensitivity chloroquine combinations). effect accompanied by dysregulation cycle, decrease reduced thiols, depolarization mitochondrial membrane level p44/p42 MAPK. Both inhibitors have ability induce apoptosis. Differences LC3A/B LC3B proteins between samples indicate these drugs inhibit at different stages. enhancement suggests possibility combining anti-cancer potential modulators process.

Language: Английский

Crosstalk Between Autophagy and Oxidative Stress in Hematological Malignancies: Mechanisms, Implications, and Therapeutic Potential DOI Creative Commons
Antonio José Cabrera-Serrano, José Manuel Sánchez‐Maldonado, Carmen González‐Olmedo

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 264 - 264

Published: Feb. 25, 2025

Autophagy is a fundamental cellular process that maintains homeostasis by degrading damaged components and regulating stress responses. It plays crucial role in cancer biology, including tumor progression, metastasis, therapeutic resistance. Oxidative stress, similarly, key to maintaining balance oxidants antioxidants, with its disruption leading molecular damage. The interplay between autophagy oxidative particularly significant, as reactive oxygen species (ROS) act both inducers by-products of autophagy. While can function suppressor early stages, it often shifts pro-tumorigenic advanced disease, aiding cell survival under adverse conditions such hypoxia nutrient deprivation. This dual mediated several signaling pathways, PI3K/AKT/mTOR, AMPK, HIF-1α, which coordinate the autophagic activity ROS production. In this review, we explore mechanisms interact across different hematological malignancies. We discuss how triggers autophagy, creating feedback loop promotes survival, dysregulation leads increased accumulation, exacerbating tumorigenesis. also examine implications targeting autophagy-oxidative axis cancer. Current strategies involve modulating through specific inhibitors, enhancing levels pro-oxidant compounds, combining these approaches conventional therapies overcome drug Understanding complex relationship provides critical insights into novel aimed at improving treatment outcomes.

Language: Английский

Citations

1
The Assessment of the Effect of Autophagy Inhibitors—Chloroquine and 3-Methyladenine on the Antitumor Activity of Trametinib Against Amelanotic Melanoma Cells DOI Creative Commons
Dominika Stencel, Justyna Kowalska, Zuzanna Rzepka

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(7), P. 557 - 557

Published: April 7, 2025

Malignant melanoma, particularly amelanotic contributes to a very serious problem in public health. One way find new therapies is learn about and understand the molecular pathways that regulate cancer growth development. In case of tumor, autophagy process can lead development or inhibition cancer. This study aimed assess cytotoxicity connection trametinib (MEK1 MEK2 kinase inhibitor) with inhibitors—chloroquine (lysosomal clearance autophagosomes 3-methyladenine (phosphatidylinositol 3-kinases inhibitor), on two melanoma cell lines (C32 A-375). The results showed combination therapy had better anti-proliferative effects than alone both lines. C32 line was more sensitive treatment (alone combinations), A375 sensitivity chloroquine combinations). effect accompanied by dysregulation cycle, decrease reduced thiols, depolarization mitochondrial membrane level p44/p42 MAPK. Both inhibitors have ability induce apoptosis. Differences LC3A/B LC3B proteins between samples indicate these drugs inhibit at different stages. enhancement suggests possibility combining anti-cancer potential modulators process.

Language: Английский

Citations

0