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.