# Investigating the Potential of Propranolol as an Anti-Tumor Agent in Colorectal Cancer Cell Lines

## TL;DR

This study explores propranolol's potential as a treatment for colorectal cancer, showing it can reduce cancer cell growth and work well with chemotherapy.

## Contribution

The study demonstrates propranolol's anti-tumor effects and synergistic potential with chemotherapy in colorectal cancer cell lines.

## Key findings

- Propranolol suppressed CRC cell proliferation, induced apoptosis, and inhibited migration in a dose- and time-dependent manner.
- The combination of propranolol and capecitabine showed synergistic effects in metastatic CRC cells.
- HT-29 and SW-480 cell lines exhibited distinct sensitivities to propranolol's effects.

## Abstract

The incidence and mortality of colorectal cancer (CRC) have increased globally. Several therapeutic approaches have been suggested to address this health issue, in addition to classical methods. Propranolol (PRO) is a beta-blocker that was repurposed to treat infantile hemangiomas, and its anti-tumor activity has been reported. This study aimed to investigate the effects of PRO in a panel of CRC cell lines and its potential impact when combined with chemotherapy. The effects of PRO on cell cytotoxicity, cell morphology, colony formation, cell death induction, cell cycle, mitochondrial and intracellular reactive oxygen species (ROS), and migration were measured in all cells. CompuSyn software was utilized to assess the possible synergistic or additive interaction in the combined treatment. The results showed that PRO suppressed cell proliferation, altered cell morphology, inhibited colony formation, induced apoptosis, altered cell cycle and ROS generation, and inhibited the migration of treated cells in a cell-type-specific, time-dependent, and dose-dependent manner compared with the control. HT-29 was the most sensitive cell line to PRO in terms of cytotoxicity, apoptosis, cell cycle arrest, and ROS generation, while SW-480 was the most sensitive in terms of migration inhibition. Moreover, the PRO and capecitabine combination exhibited a synergistic effect and induced mitochondrial apoptosis in metastatic CRC cells. The data suggest that PRO could be a promising adjuvant therapy for primary and advanced CRC. This study identified variations between CRC cell lines in response to PRO, which may be related to their genetic and epigenetic differences. In addition, the findings highlight the potential of combination strategies to improve therapeutic outcomes in metastatic CRC.