Iscador Qu inhibits doxorubicin-induced senescence of MCF7 cells

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.

Synergistic growth inhibition mediated by dual PI3K/mTOR pathway targeting and genetic or direct pharmacological AKT inhibition in human glioblastoma models

“…Moreover, we noted that invasiveness was suppressed in particular by PQR309. The lack of strong caspase 3 elevation in association with increased levels of p38a Thr180/Tyr182 , a marker for senescence (Srdic‐Rajic et al ), supports the results obtained with β‐galactosidase staining and electron microscopy in vitro (Fig. d–g).…”

Thymoquinone and Costunolide Induce Extensive Apoptosis of Senescent Colon and Senescent Breast Cancer Cells

“…Higher doses of Dox induced senescence in HCT116 by doses of 1 µM for 2 h [38] and 500 nM for 4 h [39]. In the same manner, MCF7 exhibited the senescence feature when subjected to different levels of Dox such as 38 nM [40], 50 nM [29,41], 75 nM [32,42], 100 nM [2,27,28], and 500 nM [43] for 1-5 days. Also, high doses of Dox 1 µM [44] and 10 µM [45] for 2 h were used to induce senescence in a short time period.…”

Alangium longiflorum Merr. Leaf Extract Induces Apoptosis in A549 Lung Cancer Cells with Minimal NFκB Transcriptional Activation

“…DOX versus AL for inducing a senescence-like phenotype DOX inhibits cancer growth through induction of apoptosis and senescence depending on dose, cell type, and culture conditions (Marino Gammazza et al, 2017;Srdic-Rajic et al, 2017). Indeed, cells treated with DOX showed an enlarged cell phenotype in this study ( Figure 3A-B), reminiscent of senescent cells (Neurohr et al, 2019).…”

“…DOX causes topoisomerase-II inhibition, impaired DNA replication, and DNA double strand breaks (Mitry and Edwards, 2016), which can all lead to cellular senescence (Marino Gammazza et al, 2017;Fallah et al, 2019). Indeed, chronic treatment of DOX at low doses can permanently arrest proliferation in MCF-7 cancer cell lines and other cells isolated from different types of solid tumors (Chang et al, 1999;Srdic-Rajic et al, 2017). DOX induces a senescence-like phenotype in cancer cells, resulting in G2/M arrest, increased cell size, and senescence-associated beta-galactosidase activity (Marino Gammazza et al, 2017;Srdic-Rajic et al, 2017).…”

“…Indeed, chronic treatment of DOX at low doses can permanently arrest proliferation in MCF-7 cancer cell lines and other cells isolated from different types of solid tumors (Chang et al, 1999;Srdic-Rajic et al, 2017). DOX induces a senescence-like phenotype in cancer cells, resulting in G2/M arrest, increased cell size, and senescence-associated beta-galactosidase activity (Marino Gammazza et al, 2017;Srdic-Rajic et al, 2017). In this study, we showed that AL was more cytotoxic and less likely to induce cellular senescence, as supported by its high efficacy to induce acute cytotoxic versus antiproliferative activity and inability to increase number of cells with enlarged cell phenotype and gene expression of IL6.…”