Yahaira Santiago-Vázquez1, Umashankar Das2, Armando Varela-Ramirez1, Sarah T Baca1, Yoshira Ayala-Marin1, Carolina Lema3, Swagatika Das2, Alaa Baryyan2, Jonathan R Dimmock2, Renato J Aguilera1. 1. Department of Biological Sciences, Bioscience Research Building, Border Biomedical Research Center, Cytometry, Screening and Imaging Core Facility, University of Texas at El Paso, Texas, 79968, USA. 2. College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5C9, Canada. 3. Department of Biological Sciences, Bioscience Research Building, Border Biomedical Research Center, Cytometry, Screening and Imaging Core Facility, University of Texas at El Paso, Texas, 79968, USA; College of Optometry, University of Houston, 4901 Calhoun Road, Houston, TX, 77204, USA.
Abstract
BACKGROUND: A novel series of structurally divergent 1,5-diaryl-3-oxo-1,4-pentadiene analogues 1-10 displayed marked cytotoxic potencies towards a number of human leukemia/lymphoma cells. OBJECTIVE: To identify novel selective cytotoxic compounds that induce apoptosis. METHODS: The Differential Nuclear Staining (DNS) screening protocol was utilized to measure the cytotoxicity of all experimental dienones on several cancerous cells. Additionally, the selective cytotoxicity index was calculated by comparing the dienone's cytotoxicity between leukemia/lymphoma cells vs. non-cancerous cells. Furthermore, to discern whether a selected dienone induced cell death via apoptosis or necrosis on T-lymphocyte leukemia cells, diverse approaches were utilized to detect individual biochemical facets of apoptosis. RESULTS: The dienones were tested for their anti-neoplastic efficiency on human leukemia/lymphoma-derived cell lines. Special emphasis was applied on dienone 1, on the basis of its sub-micromolar cytotoxicity (CC50=0.43+0.02 μM) and high selective cytotoxicity index (11.1) exerted on T-leukemia cells. In general, dienone 1 showed the most potent cytotoxic properties as compared to other dienones and a related reference cytotoxin curcumin as well as the EF-24 curcumin analogue. Dienone 1 caused cell death by apoptosis in Jurkat cells as evidenced by inducing phosphatidylserine externalization, mitochondrial depolarization and caspase-3/7. These effects were mainly attributed to the induction of apoptotic pathways. CONCLUSION: The novel dienone 1 was found to exhibit potent anti-leukemia activity by inducing programmed cell death/apoptosis. Consequently, dionone 1 should be developed further to examine its potential efficacy to combat malignancies in a pre-clinical animal model.
BACKGROUND: A novel series of structurally divergent 1,5-diaryl-3-oxo-1,4-pentadiene analogues 1-10 displayed marked cytotoxic potencies towards a number of humanleukemia/lymphoma cells. OBJECTIVE: To identify novel selective cytotoxic compounds that induce apoptosis. METHODS: The Differential Nuclear Staining (DNS) screening protocol was utilized to measure the cytotoxicity of all experimental dienones on several cancerous cells. Additionally, the selective cytotoxicity index was calculated by comparing the dienone's cytotoxicity between leukemia/lymphoma cells vs. non-cancerous cells. Furthermore, to discern whether a selected dienone induced cell death via apoptosis or necrosis on T-lymphocyte leukemia cells, diverse approaches were utilized to detect individual biochemical facets of apoptosis. RESULTS: The dienones were tested for their anti-neoplastic efficiency on humanleukemia/lymphoma-derived cell lines. Special emphasis was applied on dienone 1, on the basis of its sub-micromolar cytotoxicity (CC50=0.43+0.02 μM) and high selective cytotoxicity index (11.1) exerted on T-leukemia cells. In general, dienone 1 showed the most potent cytotoxic properties as compared to other dienones and a related reference cytotoxin curcumin as well as the EF-24 curcumin analogue. Dienone 1 caused cell death by apoptosis in Jurkat cells as evidenced by inducing phosphatidylserine externalization, mitochondrial depolarization and caspase-3/7. These effects were mainly attributed to the induction of apoptotic pathways. CONCLUSION: The novel dienone 1 was found to exhibit potent anti-leukemia activity by inducing programmed cell death/apoptosis. Consequently, dionone 1 should be developed further to examine its potential efficacy to combat malignancies in a pre-clinical animal model.
Authors: Jennifer Arrondeau; Hui K Gan; Albiruni R A Razak; Xavier Paoletti; Christophe Le Tourneau Journal: Discov Med Date: 2010-10 Impact factor: 2.970
Authors: Umashankar Das; Hari N Pati; Hiroshi Sakagami; Ken Hashimoto; Masami Kawase; Jan Balzarini; Erik De Clercq; Jonathan R Dimmock Journal: J Med Chem Date: 2011-04-20 Impact factor: 7.446
Authors: Swagatika Das; Umashankar Das; Armando Varela-Ramírez; Carolina Lema; Renato J Aguilera; Jan Balzarini; Erik De Clercq; Stephen G Dimmock; Dennis K J Gorecki; Jonathan R Dimmock Journal: ChemMedChem Date: 2011-08-08 Impact factor: 3.466
Authors: J Schlegel; I Peters; S Orrenius; D K Miller; N A Thornberry; T T Yamin; D W Nicholson Journal: J Biol Chem Date: 1996-01-26 Impact factor: 5.157
Authors: B Choodamani; Karla G Cano Hernandez; Sujeet Kumar; Ann Maria Tony; Austre Y Schiaffino Bustamante; Renato J Aguilera; Dominique Schols; C Gopi Mohan; Subhas S Karki Journal: Chem Biodivers Date: 2021-01-07 Impact factor: 2.408
Authors: Risa Mia Swain; Lisett Contreras; Armando Varela-Ramirez; Mohammad Hossain; Umashankar Das; Carlos A Valenzuela; Manuel L Penichet; Jonathan R Dimmock; Renato J Aguilera Journal: Invest New Drugs Date: 2022-07-06 Impact factor: 3.651
Authors: Paulina J Villanueva; Alberto Martinez; Sarah T Baca; Rebecca E DeJesus; Manuel Larragoity; Lisett Contreras; Denisse A Gutierrez; Armando Varela-Ramirez; Renato J Aguilera Journal: PLoS One Date: 2018-11-05 Impact factor: 3.240
Authors: Kinjal Lakhani; Edgar A Borrego; Karla G Cano; Jonathan R Dimmock; Renato J Aguilera; Swagatika Das; Praveen K Roayapalley; Rajendra K Sharma; Umashankar Das Journal: Medicines (Basel) Date: 2021-06-03