Application of MSCs in various neoplastic situations and permit scientists to enhance and modify these anti-neoplastic traits. Hence, several research try to declare the underlying mechanisms of anti-tumor activity of MSCs (Qiao et al., 2008; Bhoopathi et al., 2011; Mangraviti et al., 2016; Lu et al., 2019). The developing proof elucidated that MSCs’ secretome includes broad-range molecules mainly incorporated in modest extracellular vesicles (EVs). Exosomes would be the major group of EVs that play an critical part in intercellular communication, biologic processes, immunomodulation, NMDA Receptor Agonist supplier apoptosis, and angiogenesis by carrying and transferring numerous molecules for instance messenger RNAs (mRNAs), microRNAs, DNAs, proteins, and lipids (Nawaz et al., 2016). In this regard, recent research have reported that MSCs release a class of smaller peptides referred to as “antimicrobial peptides (AMPs)” (Harman et al., 2017; Yagi et al., 2020). These peptides play critical roles as the initial line of immune defense against numerous organisms, such as bacteria, fungi, and viruses (Brogden, 2005; Zhang and Gallo, 2016). Although most preclinical and clinical research have focused on the antimicrobial properties of AMPs, quite a few current pieces of investigation have proposed that AMPs also have targetedanti-neoplastic activity (Elrayess et al., 2020; Su and Chen, 2020; Swithenbank et al., 2020). AMPs specifically target cancer cells and induce numerous Nav1.3 Inhibitor supplier anticancer effects by disrupting the plasma membrane, interfering with intracellular molecular pathways, affecting the mitochondrial membrane, altering TME, and affecting immune responses. Consequently, AMPs promote apoptosis/necrosis, attenuate proliferation, angiogenic, metastasis, and multidrug resistance (MDR) in tumors (Chavakis et al., 2004; Wang et al., 2013; Kuroda et al., 2015; Jiang and L nerdal, 2017; Norouzi et al., 2018; Lv et al., 2019). Contemplating the truth that effective remedy responses rely on the interaction from the therapeutic agents with cancer cells and TME, focusing on the capacity of MSCs to produce and release AMPs and also the anticancer function of AMPs in TME could shed light on new anticancer mechanisms of MSCs (Wheeler et al., 2021). This overview summarizes the possible application of MSCsderived AMPs concerning their anticancer function. It also discusses distinctive mechanisms of anti-neoplastic effects of these AMPs. We also underlined the presence of AMPs inside the cargo of MSC-derived exosomes, the proposed part of preconditioning in growing therapeutic effects of MSCderived AMPs, as well as translational challenges of AMPs into clinical practice.Characteristics OF ANTIMICROBIAL PEPTIDESAntimicrobial peptides are a class of small host defense peptides (1050 amino acids) found in a variety of organisms, from prokaryotes to humans (Zhang and Gallo, 2016). According to the AMP database, 3,324 AMPs have been recognized as much as March 2022, amongst which 261 AMPs are listed as anticancer peptides (www.aps.unmc.edu). AMPs exhibit extraordinary physicochemical diversity in properties that construct their exclusive activities. These options primarily rely on amino acid sequences, length with the peptides, electrostatic charge on the molecules, lipid composition, hydrophobicity, amphipathicity, and spatial structural folding, like secondary structure, dynamics, and orientation (Jenssen et al., 2006; Hoskin and Ramamoorthy, 2008; Li et al., 2021). The majority of AMPs are amphipathic peptides that show a positive net charge with.