Table 3.
Senescence induction via standard breast cancer therapy.
| Drug | Cell line, (Concentrations) | Senescence Markers and Mechanism |
|---|---|---|
| doxorubicin | MCF-7, MDA-MB-231 (100 nM) | positive SA-β-gal staining, characteristic morphology, increased percentage of granular cells, γH2AX and 53BP1 foci, increased level of p-ATM and p21expression SASP: IL-8, VEGFR [25] |
| MCF-7 (1 μM) | positive SA-β-gal staining, p53/p21 pathway activation, telomere-related cytogenetic abnormalities induction [26] | |
| MCF-7, ZR-75 (1 μM) | p53/p21 pathway activation, G1 and G2 cell cycle block, increased p130 and decreased RB and p107 protein expression [27] | |
| MCF-7, T47D, HTB-122, CRL2324 (0.5 and 1 μM) | positive SA-β-gal staining, concomitant inactivation of P53 and RB genes lead to inhibition senescence [28] | |
| MCF-7, ZR-75.1 cells and a different status of p53 MMTV-Wnt1 mice | positive SA-β-gal staining, p53, and p21 pathway dependence ceased incorporating BrdU, characteristic morphology, phosphorylation of STAT3, SASP: IFNg, IL-6, CXCL2, TNFa, CXCR2, CXCL1 [29] | |
| MDA-MB-231 (250 nM), BT-549 (100 nM), MCF-7 (200 nM) | positive SA-β-gal staining, γH2AX expression, elevated p21 or p16 expression, SASP: IL-6, IL-8 (only MDA-MB-231, BT-549) [30] |
|
| etoposide | MCF-7 (2 μM) | positive SA-β-gal staining, morphology, G1 cell cycle phase block [32] |
| MCF-7 p21 (with ectopic expression of p21) (10 μM) | raised formation 53BP1 foci (24h), increased activity of SA-β-gal (5 days) [33] | |
| BRCA1-deficient (HBL100-, MCF7-, and T47D-derived clones with a silenced BRCA1) and BRCA1-proficient cells (HBL100, MCF7, and T47D) (2.5 and 5 μM) | the activity of SA-β-gal independent on BRCA1 [35] | |
| SN-38 | MCF-7 (100 ng/mL) | large, flatted, resistant to apoptosis and SA-β-gal-positive cells [32] |
| camptothecin | MCF-7, T47D, ZR-75-1 (10 μM) | positive SA-β-gal staining, the decrease in WRN expression enhanced senescence intensity [36] |
| irinotecan | MDA-MB-231, MC-7 (5 μM) | positive SA-β-gal staining, elevation level of following markers: p-ATM, percent of granularity in cells, increased in 53BP1 and γH2AX and secretion SASP: VEGF and IL-8 [25] |
| methotrexate | MCF-7 (10 μM) | positive SA-β-gal staining, p53 and p21 [61] |
| MCF-7 (2.5 μM) MDA-Mb-231 (30 μM) |
53BP1 and γH2AX foci observation, cells stained via SA-β-gal, many flatted and large cells, granularity increased, expression of p53 (phosphorylated and not unphosphorylated forms), p21, γH2AX grew, SASP: VEGF and IL-8 [25] | |
| paclitaxel | MCF-7 (3.3 nM) | positive SA-β-gal staining, elevation of p53 expression levels, decrease in pRB level [39] |
| MCF-7 (56 nM) MDA-MB-231 (5μM) |
positive SA-β-gal staining, flatted and large cells elevation of p21expresssion, γH2AX, and 53BP1 foci observation elevated expression of the following proteins: p21,p53, γH2AX, increased % of granularity in the cells, SASP: VEGF [25] |
|
| MDA-MB-231, Cal51 (75 nM) |
positive SA-β-gal staining, G2/M cell cycle block, increased of p21 and p16 expression, intensive production of EV contains drug [43] | |
| vinorelbine | MCF-7 (20 nM and 30 nM) | positive SA-β-gal staining, flattened cellular morphology, increase in p21 expression, inhibition of E2F1 and CIP2A protein expression [46] |
| vinblastine | MCF-7 (0.3 μM) | positive SA-β-gal staining, decrease in c-Jun expression, drop of AP-1 activation [47] |
| vincristine | MCF-7 (0.3 μM) | large, flatted and multinucleated cells, G2/M cell cycle block, an increase in the size of individual lysosomes and the total volume of the lysosomal compartment [49] |
| cisplatin | MDA-MB-231, MCF-7 (60 μM) | positive SA-β-gal staining, the rise in γ-H2AX level and the mRNA expression level of p21, activation ATR-Chk1 pathway via elevated REV3L expression [50] |
| olaparib | MDA-MD-231 (2.5 µM) | positive SA-β-gal staining, G2/M phase cell cycle block, decrease in DNA synthesis, drop in expression of the following genes: p21, CHK2, IL-6, IL-8, and BCL-XL [53] |
| tamoxifen | MCF-7 (0.5 μM) | positive SA-β-gal staining, YPEL3 expression dependent senescence [54] |
| MCF-7 (5 and 10μM) | positive SA-β-gal staining, decrease CK2 activity, ROS production, activation p53–p21Cip1/WAF dependent pathway [56] | |
| fulvestrant | MCF7, T47D (5, 10, 50 µM) | positive SA-β-gal staining, reduction in both ERα and MDM2 [58] |
| lapatinib neratinib | SKBR3 (250 nM), HCC1419 (250 nM), EFM-192A (250 nM), MDA-MB-361 (500 nM), MDA-MB-453 (1 µM) MCF7 (1 µM) |
positive SA-β-gal staining, increase in p15, p27 expression [59] |