Minerval induces apoptosis in Jurkat and other cancer cells.
Minerval is an oleic acid synthetic analogue that impairs lung cancer (A549) cell proliferation upon modulation of the plasma membrane lipid structure and subsequent regulation of protein kinase C localization and activity. However, this mechanism does not fully explain the regression of tumours induced by this drug in animal models of cancer. Here we show that Minerval also induced apoptosis in Jurkat T-lymphoblastic leukaemia and other cancer cells. Minerval inhibited proliferation of Jurkat cells, concomitant with a decrease of cyclin D3 and cdk2 (cyclin-dependent kinase2). In addition, the changes that induced on Jurkat cell membrane organization caused clustering (capping) of the death receptor Fas (CD95), caspase-8 activation and initiation of the extrinsic apoptosis pathway, which finally resulted in programmed cell death. The present results suggest that the intrinsic pathway (associated with caspase-9 function) was activated downstream by caspase-8. In a xenograft model of human leukaemia, Minerval also inhibited tumour progression and induced tumour cell death. Studies carried out in a wide variety of cancer cell types demonstrated that apoptosis was the main molecular mechanism triggered by Minerval. This is the first report on the pro-apoptotic activity of Minerval, and in part explains the effectiveness of this non-toxic anticancer drug and its wide spectrum against different types of cancer.
Laboratory of Molecular and Cellular Biomedicine, Department of Biology, IUNICS, University of the Balearic Islands, Spain.
Victoria
V
Llado
Antonio
A
Gutierrez
Jordi
J
Martínez
Jesús
J
Casas
Silvia
S
Terés
Mónica
M
Higuera
Antonio
A
Galmés
Carles
C
Saus
Joan
J
Besalduch
Xavier
X
Busquets
Pablo V
PV
Escribá
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056743:Cyclin D3 / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D018922:HL-60 Cells; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D019169:Jurkat Cells; D007942:Leukemia, Experimental / Q000188:drug therapy* / Q000473:pathology; D015458:Leukemia, T-Cell / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D009829:Oleic Acids / Q000494:pharmacology*; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
C497101:2-hydroxy-9-cis-octadecenoic acid; D056743:Cyclin D3; D009829:Oleic Acids; D051357:Cyclin-Dependent Kinase 2; D020169:Caspases