Sulforaphane induces p53‑deficient SW480 cell apoptosis via the ROS‑MAPK signaling pathway

Area of Science:

• Molecular Biology
• Cancer Research
• Cell Biology

Background:

• Sulforaphane (SFN) exhibits anticancer properties by inhibiting cancer cell growth and inducing apoptosis.
• The precise mechanisms of SFN's anticancer effects, particularly in p53-deficient colon cancer cells, require further elucidation.
• p53-deficient SW480 cells provide a model to study SFN-induced apoptosis independent of p53.

Purpose of the Study:

• To investigate the detailed anticancer effects of SFN on p53-deficient colon cancer cells (SW480).
• To elucidate the molecular signaling pathways involved in SFN-induced apoptosis in this cellular model.
• To assess the role of reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) in SFN's effects.

Main Methods:

• Establishment of an in vitro apoptosis model using SFN-treated p53-deficient SW480 cells.
• Evaluation of apoptosis using MTT assay, flow cytometry, western blotting, and ELISA.
• Assessment of mitochondrial membrane potential, Bax/Bcl-2 ratio, caspase activation, ROS generation, and MAPK signaling (Erk/p38).

Main Results:

• SFN induced mitochondria-associated apoptosis in SW480 cells, evidenced by disrupted mitochondrial potential, increased Bax/Bcl-2 ratio, and caspase activation.
• SFN-induced apoptosis correlated with increased ROS generation and activation of Erk and p38 MAPKs.
• SFN did not induce p73 expression, and apoptosis was confirmed as ROS-dependent and mediated by Erk/p38 signaling.

Conclusions:

• SFN induces apoptosis in p53-deficient SW480 colon cancer cells through p53/p73-independent pathways.
• The mechanism involves ROS generation and activation of the Erk/p38 MAPK signaling cascade.
• SFN enhances the sensitivity of p53-proficient cells to cisplatin, suggesting potential therapeutic applications.