Gramicidin

Gramicidin is a linear polypeptide antibiotic mixture, also known as Gramicidin D (GrD), composed of Gramicidin A, Gramicidin B and Gramicidin C^[1,6]. Gramicidin molecules dimerize within lipid bilayers to form transmembrane channels permeable to monovalent cations, thereby dissipating sodium, potassium, and proton gradients, disrupting membrane potential, and impairing adenosine triphosphate (ATP) production^[1,5]. Gramicidin is used in research on antimicrobial membrane activity, ion homeostasis, cancer-cell bioenergetics and apoptosis, tumor angiogenesis, and ionophore-mediated antimalarial activity^[1-6].

In vitro, Gramicidin (0μM, 0.3μM, 1μM, and 3μM; 24h and 48h) increased apoptosis and G2/mitosis (G2/M) cell-cycle arrest and reduced migration, cyclin D1, B-cell lymphoma 2 (Bcl-2), and phosphorylated forkhead box O1 in SGC-7901 gastric cancer cells; Gramicidin produced IC₅₀ values of 0.183μM and 0.191μM in SGC-7901 and BGC-823 cells, respectively^[2]. Gramicidin (0μM, 0.33μM, 1μM, and 3μM; 24h, 48h, and 72h) reduced OVCAR8, SKOV3, and A2780 ovarian cancer cell proliferation in concentration- and time-dependent patterns; Gramicidin (0μM, 0.1μM, 0.3μM, and 1μM; 24h and 48h) increased deoxyribonucleic acid fragmentation, the sub-G1 population, caspase-3 cleavage, and poly(adenosine diphosphate-ribose) polymerase (PARP) cleavage^[3]. Gramicidin (0.04mg/mL; 24h) reduced HeLa cervical cancer cell growth by 40%, while Gramicidin (0.3mg/mL; 24h) combined with lipophilic bismuth nanoparticles (BisBAL NPs) (1μM, 10μM, 25μM, 50μM, 100μM, and 150μM) increased growth inhibition to 86% from 10μM BisBAL NPs and disrupted cell-membrane integrity^[4].

In vivo, Gramicidin A, the predominant component of Gramicidin (0.11mg/kg; intratumoral injection twice weekly for 14 days), reduced mean tumor mass by approximately 40% in female hairless Nu/J mice bearing SN12C renal cell carcinoma xenografts without a significant change in body weight^[5]. Gramicidin (1.4mg/kg/day; intraperitoneal injection once daily for 4 days) reduced parasitemia in Plasmodium vinckei petteri-infected mice with ED₅₀ of 1.4mg/kg/day^[6].

References:
[1] Ragioto DAMT, Carrasco LDM, Carmona-Ribeiro AM. Novel gramicidin formulations in cationic lipid as broad-spectrum microbicidal agents. Int J Nanomedicine. 2014;9:3183-3192. doi:10.2147/IJN.S65289.
[2] Chen T, Wang Y, Yang Y, Yu K, Cao X, Su F, et al. Gramicidin inhibits human gastric cancer cell proliferation, cell cycle and induced apoptosis. Biol Res. 2019;52(1):57. doi:10.1186/s40659-019-0264-1.
[3] Choi MS, Lee CY, Kim JH, Lee YM, Lee S, Kim HJ, et al. Gramicidin, a bactericidal antibiotic, is an antiproliferative agent for ovarian cancer cells. Medicina (Kaunas). 2023;59(12):2059. doi:10.3390/medicina59122059.
[4] Cabral-Romero C, García-Cuellar CM, Hernandez-Delgadillo R, Sánchez-Pérez Y, Meester I, Solís-Soto JM, et al. Synergistic antitumor activity of gramicidin/lipophilic bismuth nanoparticles (BisBAL NPs) on human cervical tumor cells. Front Nanotechnol. 2021;3:633604. doi:10.3389/fnano.2021.633604.
[5] David JM, Owens TA, Barwe SP, Rajasekaran AK. Gramicidin A induces metabolic dysfunction and energy depletion leading to cell death in renal cell carcinoma cells. Mol Cancer Ther. 2013;12(11):2296-2307. doi:10.1158/1535-7163.MCT-13-0445.
[6] Gumila C, Ancelin ML, Delort AM, Jeminet G, Vial HJ. Characterization of the potent in vitro and in vivo antimalarial activities of ionophore compounds. Antimicrob Agents Chemother. 1997;41(3):523-529. doi:10.1128/AAC.41.3.523.