Zidovudine, abacavir and lamivudine increase the radiosensitivity of human esophageal squamous cancer cell lines

Abstract

Telomerase is a type of reverse transcriptase that is overexpressed in almost all human tumor cells, but not in normal tissues, which provides an opportunity for radiosensitization targeting telomerase. Zidovudine, abacavir and lamivudine are reverse transcriptase inhibitors that have been applied in clinical practice for several years. We sought to explore the radiosensitization effect of these three drugs on human esophageal cancer cell lines. Eca109 and Eca9706 cells were treated with zidovudine, abacavir and lamivudine for 48 h before irradiation was administered. Samples were collected 1 h after irradiation. Clonal efficiency assay was used to evaluate the effect of the combination of these drugs with radiation doses of 2, 4, 6 and 8 Gy. DNA damage was measured by comet assay. Telomerase activity (TA) and relative telomere length (TL) were detected and evaluated by real-time PCR. Apoptosis rates were assessed by flow cytometric analysis. The results showed that all the drugs tested sensitized the esophageal squamous cell carcinoma (ESCC) cell lines to radiation through an increase in radiation-induced DNA damage and cell apoptosis, deregulation of TA and decreasing the shortened TL caused by radiation. Each of the drugs investigated (zidovudine, abacavir and lamivudine) could be used for sensitizing human esophageal cancer cell lines to radiation. Consequently, the present study supports the potential of these three drugs as therapeutic agents for the radiosensitization of esophageal squamous cell cancer.

Putative Repurposing of Lamivudine, a Nucleoside/Nucleotide Analogue and Antiretroviral to Improve the Outcome of Cancer and COVID-19 Patients

“…The next question was whether other ANNAs such as Lamivudine and/or Abacavir could exert a similar radiosensitization effect in cancer cells. Therefore, some other researchers such as Chen et al (41), returned to this idea and assayed the effect of Zidovudine, Abacavir, and Lamivudine as radiosensitizers on human esophageal cancer cells, finding that preincubation with these three ANNAs increased the radiosensitivity of the esophageal cancer cells, through an increase in DNA damage by radiation, increased apoptosis, deregulation of telomerase activity, and by decreasing the length of the telomeres as induced by radiation (41,42). These results support the hypothesis that ANNAs work as telomerase inhibitors and the resultant radiosensitization, could improve the outcomes in cancer patients exposed to radiotherapy.…”

“…However, more recently, some research groups have reported that ANNAs may not only prevent the development of viral-associated cancers, but that they have a direct effect on neoplastic processes. These recent reports tested the effect of Zidovudine, Abacavir, and Lamivudine on the growth of cancerous cells in vitro ( 41 ). The rationale behind these assays is that most if not all cancerous cells, exhibit a shortening in the length of their telomeres and an increase in telomerase activity.…”

Favipiravir, an antiviral drug, in combination with tamoxifen exerts synergistic effect in tamoxifen-resistant breast cancer cells via hTERT inhibition

“…The role of some antivirals such as zidovudine, abacavir and lamivudine in sensitization of cancer cell lines to radiation was previously reported 38 , yet the effect of FAV on cancer cells and its mechanism of action was not yet investigated. Therefore, the present study focuses on investigating for the first time the proposed role of FAV alone and its combination with TAM in inducing breast cancer cell death in TAM-resistant MCF-7 breast cancer cell lines (TAMR-1).…”

Drug repurposing: re-inventing therapies for cancer without re-entering the development pipeline—a review

“…This drug also tends to show anti-cancer effects against a number of cancer types like leukemia, lymphoma, Kaposi sarcoma, and pancreatic cancer [ 79 ]. A rise in telomerase activity, as well as inhibition, is observed in cancer cells, which leads to apoptosis [ 79 , 80 ]. Brivudine, an anti-viral drug used for herpes simplex virus, too showed anti-cancer properties by suppressing the chemoresistance [ 75 ].…”

“…Lamivudine, another anti-viral medication that may be able to prevent cancers from developing drug resistance. This drug’s efficacy as a therapeutic agent for radio sensitization of esophageal squamous cell carcinoma has been demonstrated in one study [ 90 ]. Combining lamivudine with standard chemotherapeutic drugs may contribute, to decrease tumor cell development and spread to other regions of the body and a phase 2 trial of the same is ongoing as well [ 91 ].…”