The Induction of G2/M Phase Cell Cycle Arrest and Apoptosis by the Chalcone Derivative 1C in Sensitive and Resistant Ovarian Cancer Cells Is Associated with ROS Generation

Author:

Salanci Šimon1,Vilková Mária2ORCID,Martinez Lola3,Mirossay Ladislav1,Michalková Radka1ORCID,Mojžiš Ján1ORCID

Affiliation:

1. Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, Slovakia

2. Institute of Chemistry, Faculty of Science, Pavol Jozef Šafárik University, 040 01 Košice, Slovakia

3. Flow Cytometry Unit, Biotechnology Programme, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain

Abstract

Ovarian cancer ranks among the most severe forms of cancer affecting the female reproductive organs, posing a significant clinical challenge primarily due to the development of resistance to conventional therapies. This study investigated the effects of the chalcone derivative 1C on sensitive (A2780) and cisplatin-resistant (A2780cis) ovarian cancer cell lines. Our findings revealed that 1C suppressed cell viability, induced cell cycle arrest at the G2/M phase, and triggered apoptosis in both cell lines. These effects are closely associated with generating reactive oxygen species (ROS). Mechanistically, 1C induced DNA damage, modulated the activity of p21, PCNA, and phosphorylation of Rb and Bad proteins, as well as cleaved PARP. Moreover, it modulated Akt, Erk1/2, and NF-κB signaling pathways. Interestingly, we observed differential effects of 1C on Nrf2 levels between sensitive and resistant cells. While 1C increased Nrf2 levels in sensitive cells after 12 h and decreased them after 48 h, the opposite effect was observed in resistant cells. Notably, most of these effects were suppressed by the potent antioxidant N-acetylcysteine (NAC), underscoring the crucial role of ROS in 1C-induced antiproliferative activity. Moreover, we suggest that modulation of Nrf2 levels can, at least partially, contribute to the antiproliferative effect of chalcone 1C.

Funder

Grant Agency of the Ministry of the Education, Science, Research and Sport of the Slovak Republic VEGA

Slovak Research and Development Agency

Open scientific community for modern interdisciplinary research in medicine

Medicínsky univerzitný vedecký park v Košiciach

Publisher

MDPI AG

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