2. Academic Validation
  3. Ergolide, a potent sesquiterpene lactone induces cell cycle arrest along with ROS-dependent apoptosis and potentiates vincristine cytotoxicity in ALL cell lines

Ergolide, a potent sesquiterpene lactone induces cell cycle arrest along with ROS-dependent apoptosis and potentiates vincristine cytotoxicity in ALL cell lines

  • J Ethnopharmacol. 2020 May 10:253:112504. doi: 10.1016/j.jep.2019.112504.
Amir Yami 1,  Maryam Hamzeloo-Moghadam 2,  Arezoo Darbandi 3,  Afshin Karami 4,  Pargol Mashati 4,  Vahideh Takhviji 4,  Ahmad Gharehbaghian 5
Affiliations

Affiliations

  • 1 Department of Laboratory Hematology and Blood Bank, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: [email protected].
  • 2 Traditional Medicine and Materia Medica Research Center, Shahid Beheshti University of Medical Sciences and Department of Traditional Pharmacy, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • 3 Master of Hematology and Blood Banking in High Institute of Research and Education in Transfusion Medicine Iranian Blood Transfusion Organization, Tehran, Iran.
  • 4 Department of Laboratory Hematology and Blood Bank, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • 5 Department of Laboratory Hematology and Blood Bank, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Pediatric Congenital Hematologic Disorders Research Center, Shahid Beheshti University of Medical Science, Iran. Electronic address: [email protected].
PMID: 31904493 DOI: 10.1016/j.jep.2019.112504
Abstract

Ethnopharmacological relevance: Inula oculus christi belongs to the family of Asteraceae and it was traditionally wide used in treatment of kidney stones and urethra infection; besides, recently the potent sesquiterpene lactones isolated from inula species has gained increasing attention in Cancer treatments. This study investigates the anti-cancer properties and underlying mechanism of ergolide isolated from Inula oculus christi against leukemic cell lines.

Methods: Viability, metabolic activity and proliferation evaluated using different index of MTT assay such as IC50 and GI50. Human erythrocytes were used to evaluate hemolytic activity. Flow-cytometry was used to detect and measure ROS level, and the induction of Apoptosis and Autophagy were evaluated using Annexin V/PI, Acridine Orange staining, respectively. Moreover, qRT-PCR was performed to examine the expression of a large cohort of crucial regulatory genes. Tunel assay was also carried out to assess morphologically ergolide effects.

Results: Ergolide did not exert ant cytotoxicity against non-tumorous cells and did not cause noticeable hemolysis. It also caused ROS production during early hours after treatment of cells which was then followed by cell cycle arrest in G0/G1 phase and Autophagy induction. Using N-acetyl-L-cysteine (NAC), we found that ergolide could not increase ROS and induce Autophagy and moreover repressed cell death, indicating that ergolide induce cell death through ROS-dependent manner by altering the expression of pro apoptotic related genes. Autophagy inhibition also potentiated ergolide-induced cell death. Furthermore, ergolide intensified vincristine cytotoxicity against acute lymphoblastic leukemia (ALL) cell lines revealed robust synergistic properties of ergolide with VCR.

Conclusion: Here we showed that ergolide could be considered as a potent natural compound against leukemic cells by inducing cell cycle arrest followed by dose-dependent cell death. Based on results, Autophagy response in a result of ROS accumulation acted as a survival pathway and blocking this pathway could noticeably increase ergolide cytotoxicity on ALL cell lines.

Keywords

Anti-cancer; Apoptosis; Ergolide; Selective; Sesquiterpene lactone.

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