Colorectal cancer treatment using bacteria: focus on molecular mechanisms

Abstract

Background: Colorectal cancer which is related to genetic and environmental risk factors, is among the most prevalent life-threatening cancers. Although several pathogenic bacteria are associated with colorectal cancer etiology, some others are considered as highly selective therapeutic agents in colorectal cancer. Nowadays, researchers are concentrating on bacteriotherapy as a novel effective therapeutic method with fewer or no side effects to pay the way of cancer therapy. The introduction of advanced and successful strategies in bacterial colorectal cancer therapy could be useful to identify new promising treatment strategies for colorectal cancer patients.

Main text: In this article, we scrutinized the beneficial effects of bacterial therapy in colorectal cancer amelioration focusing on different strategies to use a complete bacterial cell or bacterial-related biotherapeutics including toxins, bacteriocins, and other bacterial peptides and proteins. In addition, the utilization of bacteria as carriers for gene delivery or other known active ingredients in colorectal cancer therapy are reviewed and ultimately, the molecular mechanisms targeted by the bacterial treatment in the colorectal cancer tumors are detailed.

Conclusions: Application of the bacterial instrument in cancer treatment is on its way through becoming a promising method of colorectal cancer targeted therapy with numerous successful studies and may someday be a practical strategy for cancer treatment, particularly colorectal cancer.

Keywords: Bacterial peptides; Bacteriocins; Biotherapeutical toxins; Colorectal cancer.

Fig. 1

The colorectal cancer bacterial therapy can be performed by means of bacterial whole cell such as probiotics or bacterial-associated peptides like bacteriocins or bacterial toxins. The anticancer effect of this treatment can be achieved by different mechanisms: 1) Pore forming in the cell membrane 2) Induction of apoptosis 3) DNA alkylation 4) RNase activity 5) TNF-α production 6) Inhibition of metastasis [10, 29]

Fig. 2

Four different structure of Lucentamycins including Lucentamycins A, B, C and D [53]

Fig. 3

Some of the underlying molecular mechanisms for colorectal cancer bacteriotherapy. The whole cell bacteria (especially Lactic acid bacteria known as LABs) may lead cancer cells to apoptosis through intrinsic or extrinsic pathways. Bacterial peptides such as arenamides can prevent TNF-induced expression of pro-inflammatory mediators by NF-κB pathway blockage. Bacterial toxins such as C. perfringens enterotoxin (CPE) can directly interact with claudin-3 and claudin-4, which are over-expressed in colorectal cancerous cell membrane. This attachment results in pore formation through the membrane and cell death due to loss of cellular osmotic equilibrium. Another mechanism for bacterial toxins’ anti-cancer effect is cytotoxicity through apoptosis intrinsic pathway. Bacteriocins such as nisin are able to form membrane-pores when they bind to special type of cell surface receptors which cause leakage of cellular content and cell death. Besides pore formation activity, bacteriocins may act as apoptosis initiator through the intrinsic pathway [10, 16, 30, 50, 65, 68, 69]