Exploring the Anti‐Cancer Properties of Efavirenz, in Comparison to Thalidomide

Abstract

IntroductionIt has been suggested that “highly active antiretroviral therapy” (HAART) caused resolution of secondary pulmonary cancers. The question then is: ‘Do antiretroviral drugs (ARD) possess anti‐cancer properties, and if so, then how? Efavirenz, a Non‐Nucleoside Reverse Transcriptase Inhibitor (NNRTI) and a first line drug used to manage HIV‐1 infection in both adults and children, is hereby investigated, in comparison with the known anti‐angiogenic and anti‐cancer drug, thalidomide.MethodologyEmbryonic CAMs of 30 fertile eggs of the domestic fowl (Gallus gallus variant Domesticus) were used as in vivo vascular test environment as follows: they were randomly allocated (n=6) to Human recombinant VEGF (R&D Systems), Thalidomide (Sigma‐Aldrich), Control 1 group treated with 70% ethanol (diluent), Control 2 group of embryos that were not manipulated and Efavirenz, (Sequoia Research Products).ResultsEfavirenz suppressed angiogenesis in Chick CAM in 100% of the subjects, showing more anti‐angiogenic properties than thalidomide. Embryonic viability (as a product of CAM angiogenesis) in all the experimental groups (n=6) was as follows: Control 6 (100%); VEGF 5 (83.3%); Thalidomide 1 (17%) and Efavirenz 0 (0.0%). Thalidomide failed to suppress angiogenesis in 17% of the subjects. Moreover, unlike thalidomide, Efavirenz also suppressed erythropoiesis.Discussion and ConclusionThe role of vascular endothelial growth factor (VEGF) in both developmental and pathological angiogenesis has been studied (e.g. Ferrara, 2000; Hagedorn et al. 2004; Losordo et al., 2004; Maharaj, 2006; Makanya et al., 2007). VEGF is a specific and potent mitogen for endothelial cells that is expressed in a distinct temporo‐spatial pattern during mammalian lung development. Since cancer cell growth and viability depends on neo‐vascularization, this property of Efavirenz, which is antagonistic to VEGF activities, may cause spontaneous resolution of HIV‐associated cancers in patients placed on HAART. In a future work, the mechanism of action of this notable ARD will be further investigated.Support or Funding InformationSupported by Sefako Makgatho Health Sciences University (SMU), Ga‐Rankuwa, Gauteng province of South Africa CAM Images CAM IMAGESCAM ImagesFigure 1 Results Group Mean Angiogenic effect Standard Deviation F P‐value VEGF 0.83 0.41 Thalidomide 0.17 0.41 9.306 *0.0005 Efavirenz 0 0 Control 1 0.67 0.52 Control 2 1 0 *indicates the p value is significant, p < 0.005. Possessing 17% angiogenicity implies the thalidomide failed as an anti‐angiogenic drug in the one embryo. Moreover, one of the embryos the thalidomide group reached the end of the experiment but died within seconds of exposure. CAM had one short thriving blood vessel on the CAM surface. In Efavirenz‐treated CAMS, no blood vessels were seen and neither was there any sign of erythropoiesis.