Emetine in Combination with Chloroquine Induces Oncolytic Potential of HIV-1-Based Lentiviral Particles

Abstract

Chloroquine and Emetine are drugs used to treat human parasitic infections. In addition, it has been shown that these drugs have an antiviral effect. Both drugs were also found to cause a suppressive effect on the growth of cancer cells of different origins. Here, using the replication-deficient HIV-1-based lentiviral vector particles, we evaluated the ability of the combination of these drugs to reduce viral transduction efficiency. We showed that these drugs act synergistically to decrease cancer cell growth when added in combination with medium containing lentiviral particles. We found that the combination of these drugs with lentiviral particles decreases the viability of treated cells. Taken together, we state the oncolytic potential of the medium containing HIV-1-based particles provoked by the combination of Chloroquine and Emetine.

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“…VSV-G pseudotyped replication-defective lentiviral particles with eGFP marker gene were obtained via calcium phosphate transfection of HEK293T packaging cells (ProFection ® Mammalian Transfection System, Promega) [39,40]. HEK293T cells seeded in 100 mm Petri dishes at a density of 3 × 10 6 cells per dish were incubated for 12 h. Then cells were cotransfected with 10 µg LeGO-G2 plasmid and packaging plasmids (10 µg of pMDLg/pRRE, 5 µg of pRSV-Rev, and 2 µg VSV-G).…”

“…Apoptosis was measured by double staining with Annexin V-FITC (Invitrogene, Thermo Scientific, Waltham, MA, USA) and propidium iodide (PI) (Sigma, Cibolo, TX, USA) 72 h after transduction. To measure the distribution of cells in the phases of the cell cycle, Jurkat cells were fixed in ethanol and stained with propidium iodide [40]. All measurements were performed on an LSR Fortessa flow cytometer (BD Biosciences, San Jose, CA, USA).…”