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

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.

Encapsulation of a cationic antimicrobial peptide into self-assembled polyion complex nano-objects enhances its antitumor properties

“…Similar to our results, there were numerous tryptophan rich AMPs applied efficiently against cancer cells grown in monolayer [34][35][36][37]. However, we reported previously the effect of Gramicidn A against HT-29 spheroids showing that the peptide alone is efficient, destabilizing the spheroids, while in combination with a tumoral drug the effect is amplified [29].…”

“…Cell viability was assessed using the MTT assay as described previously [29]. After desired treatment times (24 and 48 h) the culture medium was removed from each well, MTT was added at a final concentration of 1 mg/mL and the spheroids were further incubated at 37°C for 4h.…”

Clinical Applications and Anticancer Effects of Antimicrobial Peptides: From Bench to Bedside

“…assessed the efficiency of Gramicidin A and doxorubicin against the spheroids from colorectal cancer cells. The assessment of cancer cell viability confirmed that both doxorubicin (EC50: 15.31 μg/ml) and Gramicidin A (EC50: 9.78 μM) induce cytotoxic effects against the cancer cell spheroids separately, whereas their combination reduces the cancer cell viability synergistically ( 5 ). In another study, 150 μg/ml of KT2 and RT2 inhibited the HCT-116 cell proliferation by 70.65% and 69.01%, respectively.…”

“…Along with topical administration, the safety of intravenous injection of some AMPs was evaluated. In this regard, the safety and tolerability of human lactoferrin [1][2][3][4][5][6][7][8][9][10][11] were assessed in the life-threatening infections of patients with hematological malignancies who received hematopoietic stem cell transplantation (HSCT). The results showed that patients could tolerate up to 5-mg single dose of hLF1-11 intravenously (174).…”

“…For example, drug access is restricted to the whole tumor volume due to the complexity and heterogeneity within the tumor or the surrounding microenvironment that leads to chemotherapy resistance ( 1 ). Another unpleasant problem is the lack of specificity of some anticancer drugs, which causes toxic side effects on healthy cells ( 5 , 6 ). With the advent of molecular biology, cancer treatment today has shifted from chemotherapy and radiotherapy to molecular targeting of cancer, which prevents damage to healthy tissue on the one hand and more effective treatment of cancer on the other ( 7 , 8 ).…”