RL2 Enhances the Elimination of Breast Cancer Cells by Doxorubicin

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Fabian Wohlfromm - , Otto von Guericke University Magdeburg (Author)
  • Kamil Seyrek - , Otto von Guericke University Magdeburg (Author)
  • Nikita Ivanisenko - , Otto von Guericke University Magdeburg (Author)
  • Olga Troitskaya - , Otto von Guericke University Magdeburg (Author)
  • Dagmar Kulms - , Department of Dermatology (Author)
  • Vladimir Richter - , Russian Academy of Sciences (Author)
  • Olga Koval - , Russian Academy of Sciences (Author)
  • Inna N Lavrik - , Otto von Guericke University Magdeburg (Author)

Abstract

RL2 (recombinant lactaptin 2), a recombinant analogon of the human milk protein Κ-Casein, induces mitophagy and cell death in breast carcinoma cells. Furthermore, RL2 was shown to enhance extrinsic apoptosis upon long-term treatment while inhibiting it upon short-term stimulation. However, the effects of RL2 on the action of chemotherapeutic drugs that induce the intrinsic apoptotic pathway have not been investigated to date. Here, we examined the effects of RL2 on the doxorubicin (DXR)-induced cell death in breast cancer cells with three different backgrounds. In particular, we used BT549 and MDA-MB-231 triple-negative breast cancer (TNBC) cells, T47D estrogen receptor alpha (ERα) positive cells, and SKBR3 human epidermal growth factor receptor 2 (HER2) positive cells. BT549, MDA-MB-231, and T47D cells showed a severe loss of cell viability upon RL2 treatment, accompanied by the induction of mitophagy. Furthermore, BT549, MDA-MB-231, and T47D cells could be sensitized towards DXR treatment with RL2, as evidenced by loss of cell viability. In contrast, SKBR3 cells showed almost no RL2-induced loss of cell viability when treated with RL2 alone, and RL2 did not sensitize SKBR3 cells towards DXR-mediated loss of cell viability. Bioinformatic analysis of gene expression showed an enrichment of genes controlling metabolism in SKBR3 cells compared to the other cell lines. This suggests that the metabolic status of the cells is important for their sensitivity to RL2. Taken together, we have shown that RL2 can enhance the intrinsic apoptotic pathway in TNBC and ERα-positive breast cancer cells, paving the way for the development of novel therapeutic strategies.

Details

Original languageEnglish
Article number2779
JournalCells
Volume12
Issue number24
Publication statusPublished - 6 Dec 2023
Peer-reviewedYes

External IDs

PubMedCentral PMC10741759
Scopus 85180703315
ORCID /0000-0001-6874-0548/work/151980615

Keywords

Sustainable Development Goals

Keywords

  • Apoptosis, Cell Line, Tumor, Doxorubicin/pharmacology, Estrogen Receptor alpha, Humans, Triple Negative Breast Neoplasms/drug therapy