Research on the Antitumor Activity and Mechanism of Gramicidin-S
Journal: Journal of Clinical Medicine Research DOI: 10.32629/jcmr.v7i1.5057
Abstract
Lung cancer is a malignant tumor with high morbidity and mortality worldwide, and traditional chemotherapeutic drugs such as platinum drugs (PT) and 5-fluorouracil (5-FU) are limited in their applications by drug resistance and toxic side effects, so there is an urgent need to develop new antitumor drugs that are low-toxicity, precisely targeted, and not easy to be drug-resistant. In this study, we used peptide solid-phase synthesis method to prepare Gramicidin-S (GS). We analyzed the differences in the effects of GS with PT and 5-FU through antitumor activity assay, plasma membrane depolarization assay, and scanning electron microscopy observation of cellular morphology. The results showed that GS significantly reduced A549 cell survival and rapidly induced plasma membrane depolarization, and SEM observation revealed that GS treatment severely damaged A549 cell membranes; whereas, PT and 5-FU had almost no depolarizing effect and weakly damaged cell membranes. The conclusions indicate that GS has potent cell membrane targeting on A549 lung cancer cells and exerts anti-tumor effects by destroying the cytoplasmic membrane, which provides a new direction for the research and development of targeted therapeutic drugs for lung cancer.
Keywords
Gramicidin-S; solid-phase synthesis; A549 cells; platinum drugs; 5-fluorouracil; antitumor activity; plasma membrane depolarization; scanning electron microscopy
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[10] Guan Q, Chen K, Chen Q, et al. Development of Therapeutic Gramicidin S Analogues Bearing Plastic β, γ‐Diamino Acids. ChemMedChem, 2020, 15(12): 1089-1100.
[11] Behrendt R, White P, Offer J. Advances in Fmoc solid‐phase peptide synthesis. Journal of Peptide Science, 2016, 22(1): 4-27.
[12] Chen Y L, Lin S Z, Chang J Y, et al. In vitro and in vivo studies of a novel potential anticancer agent of isochaihulactone on human lung cancer A549 cells. Biochemical Pharmacology, 2006, 72(3): 308-319.
[13] Wan Y, Stanovych A, Gori D, et al. β, γ-diamino acids as building blocks for new analogues of Gramicidin S: Synthesis and biological activity. European journal of medicinal chemistry, 2018, 149: 122-128.
[14] Hu C, Wen Q, Huang S, et al. Gramicidin‐S‐Inspired Cyclopeptidomimetics as Potent Membrane‐Active Bactericidal Agents with Therapeutic Potential. ChemMedChem, 2021, 16(2): 368-376.
[15] Baxter A A, Lay F T, Poon I K H, et al. Tumor cell membrane-targeting cationic antimicrobial peptides: novel insights into mechanisms of ac
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