Rosmarinic Acid Elicits Calcium-Dependent and Sucrose-Sensitive Eryptosis and Hemolysis through p38 MAPK, CK1α, and PKC.
chemotherapy
eryptosis
hemolysis
rosmarinic acid
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
12 Dec 2023
12 Dec 2023
Historique:
received:
05
11
2023
revised:
01
12
2023
accepted:
09
12
2023
medline:
23
12
2023
pubmed:
23
12
2023
entrez:
23
12
2023
Statut:
epublish
Résumé
Rosmarinic acid (RA) possesses promising anticancer potential, but further development of chemotherapeutic agents is hindered by their toxicity to off-target tissue. In particular, chemotherapy-related anemia is a major obstacle in cancer therapy, which may be aggravated by hemolysis and eryptosis. This work presents a toxicity assessment of RA in human RBCs and explores associated molecular mechanisms. RBCs isolated from healthy donors were treated with anticancer concentrations of RA (10-800 μM) for 24 h at 37 °C, and hemolysis and related markers were photometrically measured. Flow cytometry was used to detect canonical markers of eryptosis, including phosphatidylserine (PS) exposure by annexin-V-FITC, intracellular Ca RA elicited concentration-dependent hemolysis with AST and LDH release but rescued the cells from hypotonic lysis at sub-hemolytic concentrations. RA also significantly increased annexin-V-positive cells, which was ameliorated by extracellular Ca RA stimulates Ca
Sections du résumé
BACKGROUND
BACKGROUND
Rosmarinic acid (RA) possesses promising anticancer potential, but further development of chemotherapeutic agents is hindered by their toxicity to off-target tissue. In particular, chemotherapy-related anemia is a major obstacle in cancer therapy, which may be aggravated by hemolysis and eryptosis. This work presents a toxicity assessment of RA in human RBCs and explores associated molecular mechanisms.
METHODS
METHODS
RBCs isolated from healthy donors were treated with anticancer concentrations of RA (10-800 μM) for 24 h at 37 °C, and hemolysis and related markers were photometrically measured. Flow cytometry was used to detect canonical markers of eryptosis, including phosphatidylserine (PS) exposure by annexin-V-FITC, intracellular Ca
RESULTS
RESULTS
RA elicited concentration-dependent hemolysis with AST and LDH release but rescued the cells from hypotonic lysis at sub-hemolytic concentrations. RA also significantly increased annexin-V-positive cells, which was ameliorated by extracellular Ca
CONCLUSIONS
CONCLUSIONS
RA stimulates Ca
Identifiants
pubmed: 38138543
pii: molecules28248053
doi: 10.3390/molecules28248053
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deputyship for Research and Innovation, Ministry of Education, Saudi Arabia
ID : IFKSUDR-H236