Identifying the regulatory role of small molecule in cancer phenotypes

Abstract

Cancer developing to metastatic progression is one of the causes of lethality. In biomedical research, small molecules that modulate cell migration have great potential as anti-cancer agents and may be of direct therapeutic importance, since both tumor angiogenesis and metastasis depend on cell migration. However anti-migratory compounds are presently limited. Furthermore, there is a growing interest, in the potential benefit of combining phenotypic and targeted approach, in the quest to advance small-molecule drug discovery. Cyclic Mismatch Binding Ligands (CMBLs) are recently developed a novel class of small molecule. Anti-cancer activities of CMBLs are yet not examined. Evaluation of the effect of CMBL on cancer phenotypes along with its cellular target would provide a deeper insight into the potential of CMBL as anti-cancer drug candidates. Towards this goal, in the first part of my study, we categorized 21 CMBL analogues with respect to their ability to regulate cell migration using metastatic cervical cancer cell line CaSki by wound healing assay. Binding based screening approach using SPR already revealed the affinity for few CMBL analogues (CMBL3a and 7b) towards cellular nucleic acid target such as telomere DNA repeat. Wound healing assay already indicated the inhibitory effect of CMBL3a and 7b on CaSki cell migration. In the second part of the study we evaluated the regulatory role of CMBL3a and 7b on cell cycle and other cancer phenotypes such as cell proliferation, apoptosis and colony formation. Results suggest different modes of action for these two compounds in suppressing tumor cell growth indicating an intriguing possibility of multiple putative targets for efficiently treating tumor cell proliferation and metastases.