Biology and Medicinal Chemistry Approaches Towards Various Apoptosis Inducers

Vivek      K. Vyas; Chetan      Chintha; Mitul      R. Pandya

doi:10.2174/1871520611313030007

Abstract

Apoptosis is a genetically in-built process whereby organisms remove unwanted cells. Apoptosis can serve as a regulatory and defense mechanism in the formation of the shape and size of the human body and also to eradicate surplus amount of cells. The regulation of apoptosis is relevant and differentiates between a normal cells of body and cancer cells by loss of control. Apoptosis being an intricate process regulated by much more than just a biological mechanism. The induction of the apoptosis manifests the control on the tumour size and number of tumour cells hence establishing the application of apoptotic inducers as vital components in the treatment of cancer. During apoptosis, cells die in a controlled and regulated fashion which makes apoptosis distinct from necrosis (uncontrolled cell death). Protein components and regulators for apoptosis signaling pathways can involve the mitochondria (intrinsic pathway) or signal through death receptors (extrinsic pathway). Many different drug and gene therapy approaches are being tested for initiating apoptosis. Resistance to apoptosis is considered a hallmark of cancer. Therapeutic approaches attempted to date include traditional small molecules, antisense oligonucleotides, monoclonal antibodies, recombinant proteins and several classes of chemical compounds discussed in this review. These compounds may serve as precursor molecules for more effective drugs, all aimed at developing clinically effective therapeutics, targeting key apoptosis regulatory mechanism. This review will discuss the current understanding of apoptosis induced by various chemical agents and highlighting the role of apoptosis inducing agents as emerging opportunities for cancer therapy.

Keywords: Apoptosis, DNA damage, Caspase, Apoptosis inducers, Anticancer agents, phagocytized, phagocytes, vincristine, vinblastine, perforin-granzyme.