title: Cell penetrating peptide TAT can kill cancer cells via membrane disruption after attachment of camptothecin.
abstract: Attachment of traditional anticancer drugs to cell penetrating peptides is an effective strategy to improve their application in cancer treatment. In this study, we designed and synthesized the conjugates TAT-CPT and TAT-2CPT by attaching camptothecin (CPT) to the N-terminus of the cell penetrating peptide TAT. Interestingly, we found that TAT-CPT and especially TAT-2CPT could kill cancer cells via membrane disruption, which is similar to antimicrobial peptides. This might be because that CPT could perform as a hydrophobic residue to increase the extent of membrane insertion of TAT and the stability of the pores. In addition, TAT-CPT and TAT-2CPT could also kill cancer cells by the released CPT after they entered cells. Taken together, attachment of CPT could turn cell penetrating peptide TAT into an antimicrobial peptide with a dual mechanism of anticancer action, which presents a new strategy to develop anticancer peptides based on cell penetrating peptides.
authors.affiliation: School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Song
authors.affiliation: School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Ma
authors.affiliation: School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Bangzhi
authors.initials: B
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Beijun
authors.initials: B
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, School of Pharmacy, Lanzhou University, Lanzhou 730000, China. Electronic address: nijm@lzu.edu.cn.
authors.forename: Jingman
authors.initials: J
authors.lastname: Ni
authors.affiliation: School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, School of Pharmacy, Lanzhou University, Lanzhou 730000, China. Electronic address: wangrui@lzu.edu.cn.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002166:Camptothecin / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D010446:Peptide Fragments / Q000494:pharmacology*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D057846:Cell-Penetrating Peptides; D010446:Peptide Fragments; D054322:tat Gene Products, Human Immunodeficiency Virus; C497137:tat peptide (47-57), Human immunodeficiency virus 1; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; D002166:Camptothecin
keywords: Anticancer activity; Antimicrobial peptide; Camptothecin; Cell penetrating peptide; Membrane disruption