Reconstitution of caspase 3 sensitizes MCF-7 breast cancer cells to doxorubicin- and etoposide-induced apoptosis

MCF-7, a breast cancer-derived cell line, is deficient of caspase 3 and relatively insensitive to many chemotherapeutic agents. To study the association of caspase 3 deficiency and chemotherapeutic resistance, we reconstituted caspase 3 in MCF-7 cells and characterized their apoptotic response to do...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2001, Vol.61 (1), p.348-354
Main Authors: YANG, Xiao-He, SLADEK, Todd L, XUESONG LIU, BUTLER, Bryn R, FROELICH, Christopher J, THOR, Ann D
Format: Article
Language:English
Subjects:
Antibiotics, Antineoplastic - pharmacology
Antineoplastic agents
Antineoplastic Agents, Phytogenic - pharmacology
Apoptosis - drug effects
Apoptosis - physiology
Biological and medical sciences
Breast Neoplasms - drug therapy
Breast Neoplasms - enzymology
Breast Neoplasms - pathology
Caspase 3
Caspases - biosynthesis
Caspases - genetics
Caspases - metabolism
Caspases - physiology
Cell Nucleus - drug effects
DNA Fragmentation - drug effects
Doxorubicin - pharmacology
Drug Screening Assays, Antitumor
Enzyme Activation
Etoposide - pharmacology
General aspects
Humans
Inhibitory Concentration 50
Medical sciences
Pharmacology. Drug treatments
Tumor Cells, Cultured
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:MCF-7, a breast cancer-derived cell line, is deficient of caspase 3 and relatively insensitive to many chemotherapeutic agents. To study the association of caspase 3 deficiency and chemotherapeutic resistance, we reconstituted caspase 3 in MCF-7 cells and characterized their apoptotic response to doxorubicin and etoposide. Western blots demonstrated that caspase 3 was constitutively expressed in the reconstituted MCF-7 cells. Both morphological observation and survival assays showed that caspase 3 reconstitution significantly sensitized MCF-7 cells to both drugs. Remarkably increased activation of caspases 3, 6, and 7, cleavage of cellular death substrates, and DNA fragmentation were detected in the reconstituted MCF-7 cells after drug treatment. Together, these data demonstrated a specific role for caspase 3 in chemotherapy-induced apoptosis and in activation of caspases 6 and 7. Our results also suggest that caspase 3 deficiency may contribute to chemotherapeutic resistance in breast cancer.
ISSN:0008-5472
1538-7445