TY - JOUR
T1 - Flow cytometry-assisted quantification of cell cycle arrest in cancer cells treated with CDK4/6 inhibitors
AU - Klapp, Vanessa
AU - Bloy, Norma
AU - Jiménez-Cortegana, Carlos
AU - Buqué, Aitziber
AU - Petroni, Giulia
N1 - Funding Information:
VK is supported by the Luxembourg National Research Fund (FNR) (PRIDE19/14254520/i2TRON).
Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2024/1/30
Y1 - 2024/1/30
N2 - Cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (i.e., palbociclib, abemaciclib, and ribociclib) are well known for their capacity to mediate cytostatic effects by promoting cell cycle arrest in the G1 phase, thus inhibiting cancer cell proliferation. Cytostatic effects induced by CDK4/6 inhibitors can be transient or lead to a permanent state of cell cycle arrest, commonly defined as cellular senescence. Induction of senescence is often associated to metabolic modifications and to the acquisition of a senescence-associated secretory phenotype (SASP) by cancer cells, which in turn can promote or limit antitumor immunity (and thus the efficacy of CDK4/6 inhibitors) depending on SASP components. Thus, although accumulating evidence suggests that anti-cancer effects of CDK4/6 inhibitors also depend on the promotion of antitumor immune responses, assessing cell cycle arrest and progression in cells treated with palbociclib remains a key approach for investigating the efficacy of CDK4/6 inhibitors. Here, we describe a method to assess cell cycle distribution simultaneously with active DNA replication by flow cytometry in cultured hormone receptor-positive breast cancer MCF7 cells.
AB - Cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (i.e., palbociclib, abemaciclib, and ribociclib) are well known for their capacity to mediate cytostatic effects by promoting cell cycle arrest in the G1 phase, thus inhibiting cancer cell proliferation. Cytostatic effects induced by CDK4/6 inhibitors can be transient or lead to a permanent state of cell cycle arrest, commonly defined as cellular senescence. Induction of senescence is often associated to metabolic modifications and to the acquisition of a senescence-associated secretory phenotype (SASP) by cancer cells, which in turn can promote or limit antitumor immunity (and thus the efficacy of CDK4/6 inhibitors) depending on SASP components. Thus, although accumulating evidence suggests that anti-cancer effects of CDK4/6 inhibitors also depend on the promotion of antitumor immune responses, assessing cell cycle arrest and progression in cells treated with palbociclib remains a key approach for investigating the efficacy of CDK4/6 inhibitors. Here, we describe a method to assess cell cycle distribution simultaneously with active DNA replication by flow cytometry in cultured hormone receptor-positive breast cancer MCF7 cells.
KW - BrdU
KW - Cellular senescence
KW - MCF7
KW - Palbociclib
KW - Propidium iodide
KW - Regulated cell death
UR - http://www.scopus.com/inward/record.url?scp=85168574385&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/38302240
U2 - 10.1016/bs.mcb.2023.02.018
DO - 10.1016/bs.mcb.2023.02.018
M3 - Article
C2 - 38302240
AN - SCOPUS:85168574385
SN - 0091-679X
VL - 181
SP - 197
EP - 212
JO - Methods in Cell Biology
JF - Methods in Cell Biology
ER -