Dataset Information

A peptide-derived strategy for specifically targeting the mitochondrial-ER network of cancer cells: a new paradigm in fighting cancer

ABSTRACT: An effective anti-cancer therapy should exclusively target cancer cells and trigger in them a broad spectrum of cell death pathways that will prevent avoidance. Here, we present a novel paradigm in cancer therapy that specifically targets the mitochondria and ER of cancer cells. We developed a peptide derived from the flexible and transmembrane domains of the human protein NAF-1/CISD2. This peptide (NAF-1) specifically permeated through the plasma membranes of human epithelial breast cancer cells, abolished their mitochondrial-ER network, and triggered cell death with characteristics of apoptosis, ferroptosis and necroptosis. In vivo analysis revealed that the peptide significantly decreased tumor growth in mice carrying xenograft human tumors. Computational simulations of cancer vs. normal cells membranes revealed that the specificity of the peptide to cancer cells is due to its selective recognition of their membrane composition. NAF-1 represents therefore a promising anti-cancer lead compound that acts via a unique mechanism.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Pei Liu

LAB HEAD: Ron Mittler

PROVIDER: PXD030509 | Pride | 2022-08-12

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20211217_110132_Mittler_DIA_MCF-MCA.sne	Other
	PTC-DIA-S1-halfuL_321.d.zip	Other
	PTC-DIA-S10_288.d.zip	Other
	PTC-DIA-S11_289.d.zip	Other
	PTC-DIA-S12_290.d.zip	Other

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Publications

A peptide-derived strategy for specifically targeting the mitochondria and ER of cancer cells: a new approach in fighting cancer.

Sohn Yang Sung YS Losub-Amir Anat A Cardenas Alfredo E AE Karmi Ola O Yahana Merav Darash MD Gruman Tal T Rowland Linda L Marjault Henri-Baptiste HB Webb Lauren J LJ Mittler Ron R Elber Ron R Friedler Assaf A Nechushtai Rachel R

Chemical science 20220526 23

An effective anti-cancer therapy should exclusively target cancer cells and trigger in them a broad spectrum of cell death pathways that will prevent avoidance. Here, we present a new approach in cancer therapy that specifically targets the mitochondria and ER of cancer cells. We developed a peptide derived from the flexible and transmembrane domains of the human protein NAF-1/CISD2. This peptide (NAF-1<sup>44-67</sup>) specifically permeates through the plasma membranes of human epithelial brea ...[more]

PMID: 35774163

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