# Dual Topoisomerase Inhibitor Is Highly Potent and Improves Antitumor Response to Radiotherapy in Cervical Carcinoma

## TL;DR

A new drug called P8-D6 shows strong potential in fighting cervical cancer by boosting the effects of radiotherapy and causing cancer cell death more effectively than current treatments.

## Contribution

The study introduces P8-D6, a dual topoisomerase inhibitor with superior radiosensitizing and cytotoxic properties for cervical carcinoma treatment.

## Key findings

- P8-D6 induced significantly higher cytotoxicity and apoptosis than cisplatin in both 2D and 3D cervical cancer cell cultures.
- P8-D6 demonstrated stronger anti-proliferative effects and caused morphological changes and membrane integrity loss in 3D spheroids.
- P8-D6 acted as a more effective radiosensitizer compared to cisplatin, improving radiotherapy outcomes.

## Abstract

Despite advances in vaccination and early detection, the total number of cases and deaths from cervical cancer has risen steadily in recent decades, making it the fourth most common type of cancer in women worldwide. Low-income countries in particular struggle with limited resources and treatment limitations for cervical cancer. Thus, effective medicines that are simple to manufacture are needed. The newly developed dual topoisomerase inhibitor P8-D6, with its outstanding ability to induce apoptosis, could be a promising option. In this study, the efficacy of P8-D6 in combination with radiochemotherapy against cervical carcinoma was investigated in established cell lines and in a translational approach in ex vivo patient cells by measuring the cytotoxicity, cell viability and caspase activity in vitro in 2D and 3D cell cultures. Treatment with P8-D6 resulted in significantly greater cytotoxicity and apoptosis induction compared to standard therapeutic cisplatin in both 2D and 3D cell cultures. Specifically, a considerably stronger anti-proliferative effect was observed. The treatment also led to morphological changes and a loss of membrane integrity in the 3D spheroids. Radiotherapy also benefited greatly from P8-D6 treatment. In fact, P8-D6 was a more potent radiosensitizer than cisplatin. Simple synthesis, favorable physicochemical properties and high potency make P8-D6 a promising cervical cancer drug candidate.