6 Shogaol Induced Paraptosis A Novel Way to Target Cancer Cell Death

Abstract

Programmed cell death plays a significant role in multicellular organisms during their early phase of growth and development and in their adult life by regulating cellular homeostasis. Cell death also protects the organism by ensuring the removal of damaged, diseased, aged, infected or mutated cells. Apoptosis, autophagy and necrosis have been considered as the classic forms of cell death. Apoptosis has been a widely and extensively studied form of death. It was Kerr, Wyllie, and Currie who coined the term and#8215;Apoptosis to describe the morphological processes leading to controlled cellular self-destruction (1). Genetic studies in C elegans by Horvitz and colleagues led to the molecular level characterization of apoptosis. It revealed that the apoptotic machinery is conserved through evolution from worms to mammals with ced-9, ced-4, ced-3 homologous to the bcl-2, apaf-1 and caspase-9 genes respectively. Caspases, which are cysteine proteases, are the key enzymes which carry out the death process. However, recent studies suggest the existence of caspase independent cell death (CICD) pathways which demonstrate that cell death can occur without the involvement of caspases. It was found that caspase inhibition and apaf-1 knockout could not completely prevent the loss of interdigital web. These studies showed that CICD pathways do occur in in vivo systems, specially as a backup for apoptosis or when the apoptotic machinery fails (2, 3). These pathways are driven by proteases other than caspases, such as calpains, cathepsins etc. Most of the chemotherapeutic drugs in use trigger apoptosis but the cancer cells harbor mutations in genes involved in the apoptotic pathway thus posing a threat to flourish in the body. This prompts the necessity for the identification of agents that can trigger CICD pathways. Paraptosis is a caspase independent form of death which does not show the features of apoptosis. Formation of cytoplasmic vacuoles which are of endoplasmic reticulum and mitochondrial (abstract attached).