RL2 Enhances the Elimination of Breast Cancer Cells by Doxorubicin | Sciact

RL2 Enhances the Elimination of Breast Cancer Cells by Doxorubicin Научная публикация

Журнал

Cells
ISSN: 2073-4409

Вых. Данные

Год: 2023, Том: 12, Номер: 24, Страницы: 2779-2779 Страниц : 1 DOI: 10.3390/cells12242779

Ключевые слова

RL2; breast cancer; DXR; mitophagy; intrinsic cell death; lactaptin; K-Casein

Авторы

Wohlfromm Fabian ¹ , Seyrek Kamil ¹ , Ivanisenko Nikita V. ¹ , Troitskaya Olga ¹ , Kulms Dagmar ^2,3 , Richter Vladimir A. ⁴ , Koval Olga ⁴ , Lavrik Inna N. ¹

Организации

1	Translational Inflammation Research, Medical Faculty, Center of Dynamic Systems (CDS), Otto von Guericke University, 39120 Magdeburg, Germany
2	Experimental Dermatology, Department of Dermatology, TU-Dresden, 01307 Dresden, Germany
3	National Center for Tumor Diseases, TU-Dresden, 01307 Dresden, Germany
4	Department of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences (SB RAS), 630090 Novosibirsk, Russia

RL2 (recombinant lactaptin 2), a recombinant analogon of the human milk protein K-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.

Wohlfromm F. , Seyrek K. , Ivanisenko N.V. , Troitskaya O. , Kulms D. , Richter V.A. , Koval O. , Lavrik I.N.
RL2 Enhances the Elimination of Breast Cancer Cells by Doxorubicin
Cells. 2023. V.12. N24. P.2779-2779. DOI: 10.3390/cells12242779 WOS Scopus OpenAlex

Опубликована в печати:

6 дек. 2023 г.

Web of science:	WOS:001132821000001
Scopus:	2-s2.0-85180703315
OpenAlex:	W4389399379

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