The Biological Functions of Antimicrobial Peptides

Antimicrobial peptides affect a vast range of biological activities in various species, including viruses, fungi, bacteria, and mammalian cells. However, the mechanism by which they use to affect biological activities is still not completely clear. In most studies, antimicrobial peptides are seen as promising antibiotic alternatives, since they have shown a wide range of antibacterial properties compared to traditional antibiotics.

Apart from being effective against bacteria, antimicrobial peptides have also shown many activities against pathogens, viruses, and fungi. For example, the human cathelicidin peptide LL37 was found to be cationic with an alpha-helical structure that has antimicrobial activity against fungi, protozoa, mold, bacteria as well as certain enveloped viruses. Antimicrobial peptides have also been shown to have inhibitory effects on DNA and RNA viruses, and this has been successfully demonstrated on hepatitis B , herpes, HIV, and influenza. Additionally, different cationic antimicrobial peptides can be used in combination with traditional antibiotics to improve the medicinal value of each and broaden the antibacterial scope of traditional antibiotics.

Antimicrobial peptides and anticancer peptides can carry out their biological functions in a variety of ways. One way through which they work stems from their ability to directly bind to the bacterial membranes of the cancer cell walls. This is generally possible due to their cationic and amphipathic nature. Usually, most of the cationic antimicrobial and anticancer peptides have positively charged amino acids with a net positive charge.

Because the normal eukaryotic cell membranes feature uncharged phospholipids and cholesterol, it is possible for antimicrobial peptides and anticancer peptides to express their antimicrobial activities without causing any detrimental effects on the normal cells. Antimicrobial peptides can bind to the membranes of the bacteria using a variety of methods, the most common ones being the carpet-like method, barrel-stave method, detergent-like model, and toroidal pore model.

The Mechanisms Deployed by Anticancer Peptides in Targeting Cancer Cells

There are many gains that have been made in treating cancer tumors. But despite these gains, there are still obstacles to overcome when it comes to controlling the progression of a tumor as well as the fatal consequences surrounding the special genetic features of most of the cancer cells and the tumor microenvironment conditions.

The main obstacle is carcinogenic initiates arising from genetic cellular characteristics that cause some cellular pathways to induce malignancy in the affected cells, such as abnormal metabolism, uncontrolled cell division, immune evasion, alteration of the cellular structure, and immortality.

Given that the plasma membrane contains the entire cell content and is the first point of contact with external factors, any changes in the plasma membrane components are vital for the process of malignancy. The structure of the plasma membrane gives a lot of respect to the fluid-mosaic pattern where proteins are flowing within the bilayer of the phospholipid layers.

With such a phenomenon, proteins have the versatility to freely rotate, move in any lateral direction, and descend or ascend within the plasma membrane layers. In as much as both the malignant and normal cells obey the fluid mosaic pattern, there are major differences that exist regarding the composition of the membranes of a normal cell and that of a malignant cell. In fact, when the tumor microenvironment is altered, which elevates reactive oxygen species, it becomes possible to dysregulate phospholipid transporters, leading to the alteration of the regular patterns of plasma membrane phospholipids.

Specifically, anionic phospholipids such as phosphatidylserine (PS) move from their inner to their outer side, leading to an extra negative charge on the membrane, hence, increasing the transmembrane potential. The changes happening to the surface of the membrane are, however, not limited only to the changes in the negative charge. Studies have shown that the membranes of a malignant cell have a more significant number of microvilli which are responsible for increasing the anchoring area of the peptides as well as the adhesion of other external molecules.

Apart from the cellular changes, it is possible for tumor progression to alter the element of the Tumor Microenvironment (TME). Studies have shown that with high and rapid consumption of nutrients, and oxygen, combined with the accumulation of other metabolic substances, it is possible to alter the development of the tumor and by doing so, it becomes compelling for the cancer cells to adopt compatible features that will allow them to overcome any undesired conditions within the TME.

For instance, it is possible for the cancer cells to reprogram their metabolic pathways through the alteration of glycolysis-related proteins where the tumor cells will resort to fermentation instead of the normal aerobic.

Additionally, it is possible for oxygen tension to affect the expression patterns of slug, and vimentin, leading to higher levels of matrix metalloproteinases (MMPs) in TME that finally results in enhanced epithelial-mesenchymal transition (EMT) as a vital factor in tumor metastasis. Hypoxia as well as other TME factors may also have the ability to increase angiogenesis through the enhancement of the expression of angiogenin, basic fibroblast growth factor, and platelet-derived growth factor.

Also, TME conditions feature numerous infiltrated or resident inflammatory cells as well as mediators responsible for taking part in a variety of neoplasm progression stages, beginning with tumor initiation to cancer promotion and invasion to the near or metastasis to distant tissue cells.

Another challenge current treatments for cancer face is chemotherapeutic drug resistance. This has always been a great hindrance when it comes to achieving the desired therapeutic outcomes with a majority of cancer treatments. Immune invasion, conditions of the TME, tumor heterogeneity, the presence of cancer stem cells and efflux pumps all point back to the resistance of the cancer cells.

Most of the drugs used for cancer treatments also end up affecting several organs within the body, leading to the development of undesirable side effects such as fatigue, chest pains, constipation, diarrhea, vomiting, pain, and rashes, among other symptoms. With the current challenges experienced by common cancer therapies, devising an appropriate and targeted treatment regime may be vital in improving the outcome of the treatments as well as increasing the quality of life for the patients.

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