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Sci Rep. 2017 Jun 19;7(1):3763. doi: 10.1038/s41598-017-03898-0.

Iscador Qu inhibits doxorubicin-induced senescence of MCF7 cells.

Author information

1
Department of Experimental Oncology, National Cancer Research Center, Belgrade, Serbia.
2
Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
3
Laboratorio de Bionanotecnologia, Universidad Bernardo O Higgins, General Gana 1780, 8370854, Santiago, Chile.
4
University Clinic for Digestive Surgery, Clinical center of Serbia, Belgrade, Serbia.
5
Medical School, University of Belgrade, Belgrade, Serbia.
6
Department of Surgery, National Cancer Research Center, Belgrade, Serbia.
7
Institute for Medical Research, Center of Research Excellence in Nutrition and Metabolism, University of Belgrade, Belgrade, Serbia.
8
Department of Experimental Oncology, National Cancer Research Center, Belgrade, Serbia. tamara.zoranovic@yahoo.com.
9
Max Plank Institute for Infection Biology, Berlin Area, Germany. tamara.zoranovic@yahoo.com.

Abstract

Chemotherapy in patients with inoperable or advanced breast cancer inevitably results in low-dose exposure of tumor-cell subset and senescence. Metabolically active senescent cells secrete multiple tumor promoting factors making their elimination a therapeutic priority. Viscum album is one of the most widely used alternative anti-cancer medicines facilitating chemotherapy tolerance of breast cancer patients. The aim of this study was to model and investigate how Viscum album extracts execute additive anti-tumor activity with low-dose Dox using ER + MCF7 breast cancer cells. We report that cotreatment of MCF7 with Viscum album and Dox abrogates G2/M cycle arrest replacing senescence with intrinsic apoptotic program. Mechanistically, this switch was associated with down-regulation of p21, p53/p73 as well as Erk1/2 and p38 activation. Our findings, therefore, identify a novel mechanistic axis of additive antitumor activity of Viscum album and low dose-Dox. In conclusion, ER + breast cancer patients may benefit from addition of Viscum album to low-dose Dox chemotherapy due to suppression of cancer cell senescence and induction of apoptosis.

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