Slow sulfide donor GYY4137 potentiates effect of paclitaxel on colorectal carcinoma cells
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
35314158
DOI
10.1016/j.ejphar.2022.174875
PII: S0014-2999(22)00136-4
Knihovny.cz E-resources
- Keywords
- Colorectal carcinoma cells, H(2)S, Paclitaxel, Slow sulfide donor GYY4137,
- MeSH
- Adenosine Triphosphate pharmacology MeSH
- Apoptosis MeSH
- Colorectal Neoplasms * pathology MeSH
- Humans MeSH
- Morpholines MeSH
- Cell Line, Tumor MeSH
- Organothiophosphorus Compounds MeSH
- Paclitaxel pharmacology MeSH
- Hydrogen Sulfide * metabolism MeSH
- Sulfides pharmacology therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Adenosine Triphosphate MeSH
- GYY 4137 MeSH Browser
- Morpholines MeSH
- Organothiophosphorus Compounds MeSH
- Paclitaxel MeSH
- Hydrogen Sulfide * MeSH
- Sulfides MeSH
Although paclitaxel (PTX) is potent chemotherapeutic agent commonly used in variety of cancers, in colorectal carcinoma its usage is excluded because of low effectivity. Up to now, some experimental attempts were utilized to improve sensitivity of colorectal carcinoma to PTX. We used a slow sulfide donor GYY4137 to increase sensitivity of colorectal carcinoma cells to PTX. As a model of colorectal carcinoma, we utilized three different cell lines - HCT116, SW620 and DLD1. We compared IC50 for PTX and PTX/GYY4137, cell cycle, apoptosis, ATP levels and changes in intracellular pH. We observed significant decrease in IC50 levels in PTX/GYY4137 groups compared to PTX in all three cell lines. PTX arrested cell cycle in G2/M phase. Differences in S phase were observed in HCT116 and DLD1 cells treated with 20 nM PTX/GYY4137, but not in SW620 cell. GYY4137 increased early, but not late phase of apoptosis. This increase was not detected in non-cancer EAHy926 cells. Upregulation of IP3R1 suggested involvement of these receptors in PTX and/or GYY4137 induced apoptosis. We also observed partial ATP depletion and intracellular acidification in PTX treated groups. In PTX/GYY4137 groups of all three cell lines no ATP depletion was detectable and intracellular acidification was lower than in PTX treated groups. Slight differences in all measured parameters were determined among HCT116, SW620 and DLD1 cells, which is probably due to physiological variations in these cells. Taking together, sensitivity of PTX to colorectal carcinoma cell lines could be increased by slow sulfide donor GYY4137, probably through potentiation of apoptosis.
References provided by Crossref.org
Signaling pathways in cutaneous wound healing