Kacar, S. | Search bioRxiv

bioRxiv2023

CURCUMIN HAS LOWER IC50 VALUES AGAINST A549 LUNG CANCER CELLS

In this study, we aimed to determine the toxic effect of curcumin on A549 lung cancer cells and to show how this effect is reflected in morphology. Firstly, the toxic doses of curcumin against A549 lung cancer cells were determined via MTT and neutral red cytotoxicity tests by using the doses of 6.25, 12.5, 25, 50, 100, 200 and 400 {micro}M. The morphological examination was performed using inverted microscope and light microscope with hematoxylin-eosin eosin.As a result, the IC50 dose of curcumin against A549 cells was 33 {micro}M according to MTT cytotoxicity test and 52 {micro}M according to the neutral red cytotoxicity test. When these doses were administered, the rounded and shrunken cells were visible in the inverted microscope, while apoptotic hallmarks such as nucleus condensation, renal nucleus structure and cellular shrinkage were detected in hematoxylin-eosin staining. In conclusion, the low IC50 values of curcumin for 24 hours indicate that curcumin is effective against A549 cells. It has the potential to be used either alone or in combination with other agents in cancer studies in case its low toxic effect on normal was assured.

pharmacology and toxicology↗

bioRxiv2023

The Prolonged Terminal Phase of Human Life Induces Survival Response in the Skin Transcriptome

Human death marks the end of organismal life under conditions such that the components of the human body continue to be alive. Such postmortem cellular survival depends on the nature (Hardy scale of slow-fast death) of human death. Slow and expected death typically results from terminal illnesses and includes a prolonged terminal phase of life. As such organismal death process unfolds, do cells of the human body adapt for postmortem cellular survival? Organs with low energy cost-of-living, such as the skin, are better suited for postmortem cellular survival. In this work, the effect of different durations of terminal phase of human life on postmortem changes in cellular gene expression was investigated using RNA sequencing data of 701 human skin samples from the Genotype-Tissue Expression (GTEx) database. Longer terminal phase (slow-death) was associated with a more robust induction of survival pathways (PI3K-Akt signaling) in postmortem skin. Such cellular survival response was associated with the upregulation of embryonic developmental transcription factors such as FOXO1, FOXO3, ATF4 and CEBPD. Upregulation of PI3K-Akt signaling was independent of sex or duration of death-related tissue ischemia. Analysis of single nucleus RNA-seq of post-mortem skin tissue specifically identified the dermal fibroblast compartment to be most resilient as marked by adaptive induction of PI3K-Akt signaling. In addition, slow death also induced angiogenic pathways in the dermal endothelial cell compartment of postmortem human skin. In contrast, specific pathways supporting functional properties of the skin as an organ were downregulated following slow death. Such pathways included melanogenesis and those representing the skin extracellular matrix (collagen expression and metabolism). Efforts to understand the significance of death as a biological variable (DABV) in influencing the transcriptomic composition of surviving component tissues has far-reaching implications including rigorous interpretation of experimental data collected from the dead and mechanisms involved in transplant-tissue obtained from dead donors.

genomics↗