Gramicidin A accumulates in mitochondria, reduces ATP levels, induces mitophagy, and inhibits cancer cell growth.

ABSTRACT: Gramicidin A (1) is a linear 15-mer peptidic natural product. Because of its sequence of alternating d- and l-chirality, 1 folds into a β^6.3-helix in a lipid bilayer and forms a head-to-head dimer to function as a transmembrane channel for monovalent cations (H⁺, Na⁺, and K⁺). The potent anticancer activity of 1 was believed to be mainly attributed to the free ion diffusion across the plasma membrane. In this study, we investigated the cytostatic action of 1 in nanomolar concentrations using the human breast cancer cell line MCF-7, and revealed the unprecedented spatiotemporal behavior of 1 for the first time. Compound 1 not only disrupted the ion concentration gradients of the plasma membrane, but also localized in the mitochondria and depolariz

SUBMITTER: Xue YW 

PROVIDER: S-EPMC9241976 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature