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Mitochondrial targeting domain of NOXA causes necrosis in apoptosis-resistant tumor cells

Dai-Trang Nguyen1, Siyuan He1, Ji-Hye Han1

  • 1Department of Biochemistry and Molecular Biology, Chosun University School of Medicine, Rm # 2219, Medical Building # 2, 309 Pilmoon-Daero, Dong-Gu, Gwang-Ju, 61452, Republic of Korea.

Amino Acids
|September 10, 2018
PubMed

Insights

A novel necrosis-inducing peptide effectively kills apoptosis-resistant tumor cells. This peptide, R8:MTD, offers a potential new strategy for treating cancers that resist conventional chemotherapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Tumor cell resistance to apoptosis-inducing agents is a significant challenge in cancer therapy.
  • Developing alternative therapeutic strategies is crucial for overcoming treatment resistance.

Purpose of the Study:

  • To investigate the efficacy of a necrosis-inducing peptide containing a mitochondria-targeting domain (MTD) against apoptosis-resistant tumor cells.
  • To evaluate the potential of R8:MTD as a novel anticancer agent for resistant cancers.

Main Methods:

  • Established doxorubicin-resistant (Dox-Res) CT26 cells.
  • Confirmed apoptosis resistance in Dox-Res cells via cell viability and caspase activation assays.
  • Administered R8:MTD peptide and assessed tumor cell necrosis, cytosolic calcium spikes, reactive oxygen species (ROS) production, and high mobility group box 1 (HMGB1) release.
  • Evaluated R8:MTD efficacy in a mouse model using Dox-Res CT26 tumor xenografts.

Main Results:

  • R8:MTD induced necrosis in Dox-Res CT26 cells.
  • Necrosis was accompanied by cytosolic calcium influx, ROS generation, and HMGB1 release.
  • R8:MTD demonstrated significant tumor-killing effects in vivo within a mouse model of resistant tumors.

Conclusions:

  • MTD-containing peptides, such as R8:MTD, can effectively eliminate tumor cells resistant to apoptosis-inducing therapies.
  • These peptides represent a promising alternative therapeutic approach for relapsed or refractory cancers.
  • Further research into MTD-containing peptides could lead to new treatments for challenging cancer types.
Keywords:
ApoptosisApoptosis-resistant cellMitochondrial targeting domainNOXANecrosisPro-necrotic peptide

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