From Antimicrobial to Anticancer Peptides: A Review

Introduction: Antimicrobial Peptides in Anticancer Therapy

• Overuse of antibiotics has led to resistant microorganisms globally.
• Antimicrobial peptides (AMPs) offer a low-antigenicity immune defense mechanism.
• AMPs are found in eukaryotic organisms, small amphipathic molecules with cationic and hydrophobic residues.
• They interact with microbial membranes, causing rapid microbe death and reducing resistance probability.
• AMPs display structural diversity: α-helical (e.g., cecropins), cysteine-rich, β-sheet AMPs (e.g., defensins).
• AMPs target bacteria, fungi, protozoa, viruses, and have potential cytotoxicity against cancer cells.

Cancer Overview

• Cancer causes death by uncontrolled growth of abnormal cells.
• Common cancers: lung, breast, colorectal.
• Current treatments like chemotherapy show low success and high side effects.
• Anticancer peptides (ACPs) are promising for selective, less harmful cancer treatment.

Anticancer Peptides (ACPs): Classification, Selectivity, and Modes of Action

• Structures: α-helical, β-sheet, and extended.
• ACPs target microbial, cancer cells, and sometimes healthy cells.
• ACPs act by membranolytic mechanisms (e.g., pore formation) or non-membranolytic mechanisms.
• Differences between cancer and normal cells aid ACP selectivity: negative charge in cancer cell membranes.

Mechanisms of Action

• Membrane disruption by ACPs can involve pore formation, apoptosis, necrosis.
• Some ACPs block angiogenesis by disrupting tumor vasculature.

ACPs for Solid and Hematological Tumors

Solid Tumors

• Solid tumors: heterogeneous cancer cell masses.
• ACPs target solid tumors via multiple mechanisms.
• Breast and prostate cancer are frequently targeted by ACPs.

Electrostatic Interactions and Activity

• Cancer cell membranes have negative charges, attracting cationic ACPs.
• Some ACPs bind to phosphatidylserine (PS) exposing membranes in cancer cells.

Mechanisms of Action: Necrosis and Apoptosis

• ACPs can penetrate cells, disrupting membranes, inducing necrosis or apoptosis.
• Some ACPs also target angiogenesis or specific molecular targets.

Hematological Tumors: Leukemias, Myelomas, and Lymphomas

• ACPs target blood, bone marrow, and lymphatic cancers.
• Electrostatic interactions aid ACP activity by targeting negatively charged cancer cell membranes.

Perspectives and Open Questions

• Designing ACPs involves balancing delivery, selectivity, and production costs.
• ACPs should have high cationicity, controlled hydrophobicity, and serum stability.
• ACPs show potential for synergy with existing chemotherapeutic agents.

Conclusion

• Anticancer peptides offer a promising new direction in cancer treatment due to their selectivity and potential for reduced side effects.
• Further research is needed in optimizing peptide design and understanding their mechanisms of action for effective cancer therapy.