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The effects of Acyclovir administration to NCI-H1975 non-small cell lung cancer cells
Serena Benedetti1, Simona Catalani1, Barbara Canonico1
1Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Saffi 2, Urbino, Italy.
Abstract:
The biochemical mechanisms by which the antiviral drug Acyclovir (ACV) may induce anticancer effects even without detecting human herpesviruses (HHVs) are still poorly understood. Herein, we investigated for the first time how NCI-H1975 non-small cell lung cancer cells responded in vitro to ACV administration by exploring mitochondrial damage and apoptosis induction. We confirmed ACV ability to cause the inhibition of cancer cell growth even without detecting intracellular HHVs; the drug also significantly inhibited the colony formation capacity of NCI-H1975 cells. Cell cycle analysis revealed an increase of the sub-G1 hypodiploid peak after ACV treatment; the activation of caspase-3 and the presence of DNA laddering sustained the capacity of the drug to induce apoptotic cell death. Regarding mitochondrial toxicity, a reduction of mitochondrial membrane potential, altered mitochondrial size and shape, and mtDNA damage were found after ACV administration. Furthermore, an increment of intracellular reactive oxygen species levels as well as the upregulation of NudT3 involved in DNA repair mechanisms were observed. Altogether, these findings suggest that mitochondria may be possible initial targets and/or sites of ACV cytotoxicity within cancer cells in the absence of intracellular HHVs.
Insights
Acyclovir (ACV) inhibits non-small cell lung cancer growth by inducing apoptosis and mitochondrial damage, independent of human herpesviruses (HHVs). This antiviral drug shows potential anticancer effects through mechanisms targeting cancer cell mitochondria.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- The anticancer mechanisms of Acyclovir (ACV) are not fully understood, especially its effects independent of human herpesviruses (HHVs).
- Investigating ACV's impact on cancer cells lacking HHVs is crucial for understanding its broader therapeutic potential.
Purpose of the Study:
- To explore the in vitro effects of Acyclovir on NCI-H1975 non-small cell lung cancer cells.
- To investigate the roles of mitochondrial damage and apoptosis induction in ACV's anticancer activity.
Main Methods:
- Cell viability and colony formation assays were performed on NCI-H1975 cells treated with ACV.
- Cell cycle analysis, caspase-3 activation assays, and DNA laddering were used to assess apoptosis.
- Mitochondrial membrane potential, morphology, mtDNA integrity, and reactive oxygen species (ROS) levels were evaluated.
Main Results:
- ACV inhibited cancer cell growth and colony formation in NCI-H1975 cells, even without detectable HHVs.
- ACV induced apoptosis, evidenced by an increase in the sub-G1 peak, caspase-3 activation, and DNA laddering.
- ACV caused mitochondrial toxicity, including reduced membrane potential, altered morphology, mtDNA damage, and increased ROS levels. NudT3 was upregulated.
Conclusions:
- Acyclovir exhibits anticancer effects on non-small cell lung cancer cells independent of HHV infection.
- Mitochondria appear to be a primary target for ACV-induced cytotoxicity in cancer cells.
- ACV's ability to induce apoptosis and mitochondrial damage suggests a novel therapeutic avenue for cancer treatment.
