Antimicrobial Peptides as New Combination Agents in Cancer Therapeutics: A Promising Protocol against HT-29 Tumoral Spheroids.

Mina Raileanu,Aurel Popescu,Mihaela Bacalum

doi:10.3390/ijms21186964

Mina Raileanu, Aurel Popescu + Show 1 more

Open Access

https://doi.org/10.3390/ijms21186964

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Abstract

Antimicrobial peptides are molecules synthetized by a large variety of organisms as an innate defense against pathogens. These natural compounds have been identified as promising alternatives to widely used molecules to treat infections and cancer cells. Antimicrobial peptides could be viewed as future chemotherapeutic alternatives, having the advantage of low propensity to drug resistance. In this study, we evaluated the efficiency of the antimicrobial peptide gramicidin A (GA) and the anticancer drug, doxorubicin (Doxo) against the spheroids from colorectal cancer cells (HT-29). The two drugs were applied separately against HT-29 spheroids as well as together to determine if they can act synergistically. The spheroid evolution, cell viability, and ATP levels were monitored at 24 and 48 h after the applied treatments. The results show significant drops in cell viability and cellular ATP levels for all the experimental treatments. The simultaneous use of the two compounds (GA and Doxo) seems to cause a synergistic effect against the spheroids.

Highlights

Despite recent advances in medical treatment, cancer still remains a worldwide leading cause of death
The results reveal that the two compounds have a cytotoxic effect against the HT-29 spheroids
We have studied the effects of gramicidin A (GA) and a known chemotherapeutic drug Doxo, administered separately and in combination, against HT-29 colorectal spheroids

Summary

Introduction

Despite recent advances in medical treatment, cancer still remains a worldwide leading cause of death. Some of the obstacles are due to intratumor complexity and heterogeneity and to cell interactions inside the tumor or with the surrounding microenvironment [1,2]. These can limit the drug access to the whole tumor volume, leading to chemotherapy resistance [1,3,4]. Another unpleasant problem comes from the lack of specificity of some of the anticancer drugs, which kill healthy cells, resulting in toxic side effects [5]

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