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

Serena Benedetti, Simona Catalani, Francesco Palma, Barbara Canonico, Francesca Luchetti, Rossella Galati, Stefano Papa, Serafina Battistelli

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Aims and methods: 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. Findings and significance: 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.

Original languageEnglish
Pages (from-to)80-85
Number of pages6
JournalLife Sciences
Volume215
DOIs
Publication statusPublished - Dec 15 2018

Fingerprint

Jurkat Cells
Acyclovir
Cytotoxicity
Cell Cycle
Leukemia
Cells
Apoptosis
Pharmaceutical Preparations
Antiviral Agents
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
DNA Fragmentation
T-cells
S Phase
Fluorouracil
Caspase 3
Cisplatin
Cell death
Neoplasms
Cell Survival
Cell Death

Keywords

  • Acyclovir
  • Adjuvant therapy
  • Apoptosis induction
  • Cell cycle perturbation
  • Jurkat leukemia cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Acyclovir induces cell cycle perturbation and apoptosis in Jurkat leukemia cells, and enhances chemotherapeutic drug cytotoxicity. / Benedetti, Serena; Catalani, Simona; Palma, Francesco; Canonico, Barbara; Luchetti, Francesca; Galati, Rossella; Papa, Stefano; Battistelli, Serafina.

In: Life Sciences, Vol. 215, 15.12.2018, p. 80-85.

Research output: Contribution to journalArticle

Benedetti, Serena ; Catalani, Simona ; Palma, Francesco ; Canonico, Barbara ; Luchetti, Francesca ; Galati, Rossella ; Papa, Stefano ; Battistelli, Serafina. / Acyclovir induces cell cycle perturbation and apoptosis in Jurkat leukemia cells, and enhances chemotherapeutic drug cytotoxicity. In: Life Sciences. 2018 ; Vol. 215. pp. 80-85.
@article{ce91eec3e7dd466c90044545ce04f0f7,
title = "Acyclovir induces cell cycle perturbation and apoptosis in Jurkat leukemia cells, and enhances chemotherapeutic drug cytotoxicity",
abstract = "Aims and methods: 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. Findings and significance: 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.",
keywords = "Acyclovir, Adjuvant therapy, Apoptosis induction, Cell cycle perturbation, Jurkat leukemia cells",
author = "Serena Benedetti and Simona Catalani and Francesco Palma and Barbara Canonico and Francesca Luchetti and Rossella Galati and Stefano Papa and Serafina Battistelli",
year = "2018",
month = "12",
day = "15",
doi = "10.1016/j.lfs.2018.11.002",
language = "English",
volume = "215",
pages = "80--85",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Acyclovir induces cell cycle perturbation and apoptosis in Jurkat leukemia cells, and enhances chemotherapeutic drug cytotoxicity

AU - Benedetti, Serena

AU - Catalani, Simona

AU - Palma, Francesco

AU - Canonico, Barbara

AU - Luchetti, Francesca

AU - Galati, Rossella

AU - Papa, Stefano

AU - Battistelli, Serafina

PY - 2018/12/15

Y1 - 2018/12/15

N2 - Aims and methods: 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. Findings and significance: 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.

AB - Aims and methods: 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. Findings and significance: 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.

KW - Acyclovir

KW - Adjuvant therapy

KW - Apoptosis induction

KW - Cell cycle perturbation

KW - Jurkat leukemia cells

UR - http://www.scopus.com/inward/record.url?scp=85056154106&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056154106&partnerID=8YFLogxK

U2 - 10.1016/j.lfs.2018.11.002

DO - 10.1016/j.lfs.2018.11.002

M3 - Article

C2 - 30403989

AN - SCOPUS:85056154106

VL - 215

SP - 80

EP - 85

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

ER -