Cryptocaryone Exhibits ROS/MAPK-Dependent Antiproliferative and Apoptosis-Inducing Effects on Triple-Negative Breast...

Area of Science:

• Biochemistry
• Molecular Biology
• Cancer Research

Background:

• Triple-negative breast cancer (TNBC) presents significant clinical challenges due to its heterogeneity and poor response to targeted therapies.
• Omics technologies reveal TNBC's molecular complexity, highlighting the need for novel therapeutic strategies.

Purpose of the Study:

• To investigate the antiproliferative effects of Cryptocaryone (CPC) on TNBC cells.
• To elucidate the molecular mechanisms underlying CPC's action, including its role in drug resistance and aggressiveness.

Main Methods:

• In vitro antiproliferative assays on TNBC and normal breast cell lines.
• In vivo tumor xenograft studies in a mouse model.
• Flow cytometry and Western blotting to assess apoptosis, oxidative stress, DNA damage, and MAPK pathway activation.

Main Results:

• CPC exhibited significant antiproliferative effects on TNBC cells (HCC1937, MDA-MB-231) with low cytotoxicity in normal cells (H184B5F5/M10).
• CPC reduced tumor growth in vivo and induced apoptosis, oxidative stress, and DNA damage in TNBC cells.
• CPC's effects were mediated through JNK and p38 MAPK activation, and N-acetylcysteine reversed CPC-induced oxidative stress.

Conclusions:

• Cryptocaryone (CPC) demonstrates potent antiproliferative activity against TNBC by inducing apoptosis and DNA damage via oxidative stress and MAPK signaling.
• CPC shows a favorable safety profile, with reduced toxicity in normal cells and a mouse model, suggesting therapeutic potential for TNBC.