1. Academic Validation
  2. Evaluating the cytotoxicity mechanism of the cell-penetrating peptide TP10 on Jurkat cells

Evaluating the cytotoxicity mechanism of the cell-penetrating peptide TP10 on Jurkat cells

  • Biochimie. 2023 Nov 2:S0300-9084(23)00293-6. doi: 10.1016/j.biochi.2023.11.001.
Kun Ji 1 Yufan Yao 2 Yuxuan Gao 2 Sujie Huang 2 Ling Ma 2 Qing Pan 1 Jun Wu 1 Wei Zhang 3 Hongmei Chen 4 Lei Zhang 5
Affiliations

Affiliations

  • 1 The First Hospital, The First Clinical Medical College, Lanzhou University, Lanzhou, 730000, China.
  • 2 School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.
  • 3 School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China; State Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Lanzhou University, Lanzhou, 730000, China. Electronic address: zhangwei@lzu.edu.cn.
  • 4 School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China. Electronic address: hmchen@lzu.edu.cn.
  • 5 The First Hospital, The First Clinical Medical College, Lanzhou University, Lanzhou, 730000, China. Electronic address: ldyy_lzhang@lzu.edu.cn.
Abstract

TP10, a classic cell-penetrating peptide, shows a high degree of similarity to AMPs in structure. Although TP10 has been widely used in drug delivery, the mechanism underlying its cytotoxicity is yet to be elucidated. Herein, we explored the cell-killing mechanism of TP10 against human leukemia Jurkat cells. TP10 induced necrosis in Jurkat cells via rapid disruption of cell membranes, particularly at high concentrations. Although mitochondria in Jurkat cells were damaged by TP10, mitochondria-mediated Apoptosis did not occur, possibly due to intracellular ATP depletion. Necroptosis in TP10-treated Jurkat cells became an alternative route of Apoptosis. Our results demonstrate that necrosis and Necroptosis rather than Apoptosis are involved in the cell-killing mechanism of TP10, which contributes to the understanding of its toxicity.

Keywords

Cell-penetrating peptide; Cytotoxicity; Membrane disruption; Necroptosis; TP10.

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