It induced G<sub>2</sub>/M phase arrest in HCT116 cells, associated with a marked decrease in cyclin B and CDK1 protein expression and increased caspase activation, PARP cleavage, chromatin condensation, and sub-G<sub>1</sub> apoptosis.
Western blot analysis also showed that the expression of proapoptotic proteins (cleaved caspase 3 and cleaved PARP) was upregulated, while that of antiapoptotic proteins (Bcl-2 and survivin) was downregulated after deguelin treatment in CRC cell lines.
Studies carried out on CRC and TA tissues revealed the overactivation of the IGF-1 receptor signalling pathway, as well as the overexpression of procaspase 3 and PARP in tumoural tissue with respect to MANC tissue.
Our findings proved that the upregulation of <i>PARP-1</i> is associated with tumor progression and poor prognosis in Saudi patients with colorectal cancer, suggesting that <i>PARP-1</i> can be novel and valuable signatures for predicting the clinical outcome of patients with colorectal cancer.
Synergism was evident between LT-626 and cisplatin, oxaliplatin and SN-38 suggesting that PARP inhibitors in combination with DNA damaging agents may be a successful strategy for treatment of CRC.
We discuss the possible rationale for combining PARP inhibition with DNA damaging agents, and we address the link between DDR and EGFR pathways in CRC.