Undergraduate Research UNLV Las Vegas, Nevada, United States
Introduction:: Cellular senescence exerts a profound influence on various aspects of cellular biology. Chemotherapeutic agents, including Palbociclib () and Doxorubicin (), have been identified as inducers of cellular senescence. Additionally, the cellular microenvironment, whether presented in a two-dimensional (2D) monolayer or a three-dimensional (3D) tissue, plays a crucial role in modulating cellular activities. The objective of this study is to quantify the alterations in organelles and cells within 2D and 3D environments, subjected to cellular senescence induced by anti-cancer drugs. To comprehensively assess these effects, we analyzed biochemical, structural, and physical characteristics, aiming to gain a deeper understanding of the implications of anti-cancer drug-induced cellular senescence in different cellular microenvironments.
Materials and Methods:: In this study, we utilized human keratinocytes (HaCaT) in both two- dimensional (2D) monolayers and three-dimensional (3D) tissues. One of the aims was to explore the concentration-dependent effects of anti-cancer medications on cellular senescence. To achieve this, cells cultivated in a 24-well plate were exposed to solutions of the anti-cancer drug Palbociclib at varying concentrations, ranging from 2.5 µM to 400 µM, as well as solutions of the anti-cancer drug Doxorubicin at concentrations ranging from 50 nM to 400 nM. The treatment of cells with Palbociclib and Doxorubicin was conducted over a 24-hour period as part of the experiment. Throughout the investigation, we employed fluorescence imaging techniques to accurately quantify the biochemical and morphological characteristics of cells and organelles.
Results, Conclusions, and Discussions:: Results: Our observations revealed notable changes in the morphological properties of cells and nuclei in both anti-cancer drug concentrations. Even at the lowest dose of Palbociclib tested (2.5 µM), there was a discernible enlargement of the nuclei compared to normal cells. Doses of 5 µM, 10 µM, 20 µM, and 40 µM of Palbociclib exhibited similar nuclei morphology, but varying cell shape and spreading area. Similarly, significant cell changes were observed compared to normal cells at Doxorubicin morphological doses of 50 nM, 100 nM, 200 nM, and 400 nM.
Conclusion: The obtained results demonstrate that anti-cancer medications exert a concentration-dependent influence on cellular and nuclear morphology.These findings highlight the complexity of the cellular response to anti-cancer drugs and underscore the need for further investigations to comprehend the underlying mechanisms and potential implications for cancer treatment strategies.
