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As part of the efforts to drug repurposing, some HIV drugs have recently been identified to exert anticancer effects. Selected nucleoside analogues of nucleosidic reverse-transcriptase inhibitors (NRTIs) have been shown to interfere with RNA transcription of HI viruses as well as with the replication of DNA in cancer cells. Non-nucleosidic reverse transcriptase inhibitors (NNRTIs) are believed to have less effects on human DNA replication and, thus, on cancer cell proliferation. Assessment of the effect of the NNRTI efavirenz in human cancer cells, however, revealed a high sensitivity of leukemia cells to this agent at pharmacologically relevant concentrations of less than 10 µg/ml. Cell death induced by efavirenz was caused by apoptosis, as shown by FACScan analysis (Annexin binding) and western blot analysis (cleavage of caspases and PARP). Western blot analyses also revealed a pronounced activation and phosphorylation of the DNA damage marker proteins p53, chk2 and H2AX, indicating DNA replication and genomic integrity as primary targets of efavirenz in leukemia cells.

Induction of DNA damage and apoptosis in human leukemia cells by efavirenz