Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, Italy.
Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, Italy.
Life Sci. 2018 Dec 15;215:80-85. doi: 10.1016/j.lfs.2018.11.002. Epub 2018 Nov 4.
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.
许多抗病毒药物已被报道具有直接的细胞毒性作用，可通过不同的机制表现出抗增殖和促凋亡作用。在本研究中，我们考虑了抗病毒药物阿昔洛韦 (ACV) 对白血病细胞的细胞毒性作用，通过研究药物给药后对三个尚未探索的细胞系（即 Jurkat、U937 和 K562）的细胞周期扰动和凋亡诱导，来评估其对三种仍未探索的细胞系的影响。同时，评估了顺铂 (CDDP) 和 5-氟尿嘧啶 (5-FU) 与 ACV 联合的细胞毒性作用，从而评估抗病毒药物是否可以增强癌细胞对这些化疗药物的敏感性。
我们的结果表明，ACV 的细胞毒性作用在 Jurkat 细胞（急性 T 细胞白血病）中最大，这些细胞在药物暴露后表现出剂量和时间依赖性的细胞活力降低。细胞周期的流式细胞术分析显示，ACV 给药后 S 期延迟/阻滞和亚 G1 峰增加，表明细胞凋亡死亡。Caspase-3 的激活和核 DNA 片段的存在证实了 ACV 处理细胞中诱导的凋亡。有趣的是，用 ACV 预处理 Jurkat 细胞 72 小时或 7 天可增加 CDDP 和 5-FU 的细胞毒性，提示增强了白血病细胞对这些抗癌药物的敏感性。
