Acyclovir induces cell cycle perturbation and apoptosis in Jurkat leukemia cells, and enhances chemotherapeutic drug cytotoxicity

• Published in: Life sciences (1973) 2018-12, Vol.215, p.80-85
• Main Authors: Benedetti, Serena, Catalani, Simona, Palma, Francesco, Canonico, Barbara, Luchetti, Francesca, Galati, Rossella, Papa, Stefano, Battistelli, Serafina
• Format: Article
• Language: English
• Subjects: Acyclovir; Acyclovir - administration & dosage; Acyclovir - pharmacology; Adjuvant therapy; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antiviral Agents - administration & dosage; Antiviral Agents - pharmacology; Apoptosis - drug effects; Apoptosis induction; Cell Cycle - drug effects; Cell cycle perturbation; Cell Survival - drug effects; Cisplatin - administration & dosage; Cisplatin - pharmacology; DNA Fragmentation - drug effects; Dose-Response Relationship, Drug; Flow Cytometry; Fluorouracil - administration & dosage; Fluorouracil - pharmacology; Humans; Jurkat Cells; Jurkat leukemia cells; K562 Cells; Leukemia - drug therapy; Leukemia - pathology; Time Factors; U937 Cells
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2018.11.002

Many antiviral agents have been reported to present direct cytotoxic activity in cancer, showing antiproliferative and proapoptotic effects through different mechanisms. In the present study, we took into account the cytotoxic action of the antiviral drug acyclovir (ACV) on leukemia cells, by investigating cell cycle perturbations and apoptosis induction upon drug administration to three still unexplored cell lines, namely Jurkat, U937, and K562. At the same time, the cytotoxicity of cisplatin (CDDP) and 5‑fluorouracil (5‑FU) in combination with ACV was assessed, thus to evaluate if the antiviral agent could enhance cancer cell sensitivity to these chemotherapeutic drugs. Our results showed that ACV cytotoxic action was maximum in Jurkat cells (acute T cell leukemia), which showed a dose- and time-dependent reduction of cell viability after drug exposure. The flow cytometric analysis of cell cycle revealed a delay/block in S phase and an increase of the sub-G1 peak upon ACV administration, thereby indicating apoptotic cell death. The activation of caspase-3 and the presence of nuclear DNA fragmentation confirmed the induction of apoptosis in ACV-treated cells. Interestingly, the pre-treatment of Jurkat cells with ACV for 72 h or 7 days increased CDDP and 5-FU cytotoxicity, suggesting enhanced leukemia cell sensitivity to these anticancer drugs.