Celecoxib induced apoptosis against different breast cancer cell lines by down-regulated NF-κB pathway

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Inducible cyclooxygenase-2 (COX-2) is frequently overexpressed in breast tumors, making it a significant therapeutic target.
• Understanding the differential response of breast cancer subtypes to targeted therapies is crucial for effective treatment strategies.

Purpose of the Study:

• To investigate the effects of Celecoxib, a COX-2 inhibitor, on two distinct molecular breast cancer subtypes: MDA-MB-231 and SK-BR-3.
• To elucidate the molecular mechanisms underlying Celecoxib's action, including its impact on cell proliferation, apoptosis, cell cycle, and key signaling pathways.

Main Methods:

• Cell viability was assessed using the MTT assay.
• Western blotting was employed to examine the expression of NF-κB (p52 and p65) and Caspase 3.
• RT-PCR was used to quantify COX-2 mRNA levels, while flow cytometry analyzed cell cycle profiles and apoptosis.

Main Results:

• Celecoxib inhibited MDA-MB-231 cell proliferation in a dose- and time-dependent manner, and SK-BR-3 cells in a dose-dependent manner.
• Apoptosis was induced in both cell lines by Celecoxib, with a greater effect observed in MDA-MB-231 cells.
• Celecoxib downregulated NF-κB and COX-2 expression while upregulating Caspase 3. Cell cycle arrest occurred at G1 phase in MDA-MB-231 and G2 phase in SK-BR-3 cells.

Conclusions:

• Celecoxib exhibits distinct effects on different breast cancer molecular subtypes.
• The findings highlight the importance of considering breast cancer subtype when developing treatment strategies involving Celecoxib.
• Targeting COX-2 with Celecoxib shows potential for subtype-specific breast cancer therapy.