NFκB, p53, p21 interacts with DNA damage indicators & Stat3 protein in inducing the radio-modulatory potential of Ethyl cinnamate on HepG2 and BRL3A cells

Ethyl cinnamate (Ethyl (2E)-3-phenylprop-2-enoate) is an aromatic compound of cinnamon. According to the Indian Ayurvedic medical system, cinnamon has been used to treat various diseases.The current study examines the potential of ethyl cinnamate (EC) in modulating radiation responses in cancerous (HepG2) and normal (BRL-3A) cells.

HepG2 and BRL3A cells were pre-treated with EC (75 µg/ml) for 24 hours before being subjected to a single 7.5 Gy dose of γ-ray. By using flow cytometry and western blotting, the primarysurvival pathways (PI3-AKT, JAK-STAT, MAPK & JNK), cell cycle inhibitors (p53 & p21), DNA damage indicators (ATM, ATR, γ-H2AX, cleaved PARP), anti-angiogenic TIMP2 and angiogenic factor MMP9 were analysed. The activity of the catalase enzyme was assessed by UV-Visible spectrophotometry.

The complex effects of EC on the suppression of pro-survival and anti-apoptotic proteins such as p-JNK, p-JAK2, p-STAT3, and p-p38MAPK results in enhanced radio-sensitization and radiation-induced cancer cell killing. The radio-response is potentiated by EC’s ability to suppress downstream effector proteins such as p21, p-p53, and MMPs and block radiation-triggered p-NF-κB signalling pathways. Additionally, EC effectively enhanced the radio-induced DNA damage in HepG2 cells by stimulating p-ATM, p-ATR, γ-H2AX and PARP cleavage. However, in BRL-3A cells, EC significantly reduced radiation-induced DNA damage.

The potential of EC as a radio-sensitizer in HepG2 cells and a radio-protector in BRL3A cells was observed in this investigation. Based on the elucidated molecular mechanisms, safety profile, and low cost, EC might be considered a promising adjuvant to enhance radio-therapeutic efficacy in cancer treatment.