Abnormal Signal Transduction via Over-expression of Pim-1 Regulated Senescence, Cell Cycle, Apoptosis and Metastatic Invasion: Novel Anticancer Targets and Their Potent Inhibitors from Marine Sources

Abstract

Existing cancer chemotherapeutics can kill normal as well as malignant cells. To solve these issues, scientists are now more concerned about the design and discovery of potential anticancer, least toxic leads, which can promote apoptosis process and inhibition of abnormal signal transduction via hyperactivation of protein kinases such as Pim-1 due to overexpression or mutation of proto-oncogenes and tumor suppressor genes related to molecular mechanisms of senescence, cell cycle, apoptosis and metastatic invasion, thus leading to anticancer activities. Natural scaffolds play a great role in this aspect. Sea is full of biodiverse natural resources of medicinal compounds derived from marine plants, sponges, actinomycetes, cynobacteria, fungi, corals and animals. Many anticancer compounds were successfully discovered. But there are few potent compounds developed against abnormal signal transduction mechanism. Therefore, an attempt has been made in the present review to focus on molecular mechanisms of various targets in connection with the over-expression of Pim-1 mediated senescence, cell cycle, apoptosis and metastatic invasion and their potent inhibitors. Biochemical mechanisms of the potent marine sourced inhibitors keeping activities against abnormal signal transduction were discussed in this study. It gives great attention to expand the capabilities in these upcoming areas to remain globally relevant. Existed marine sourced anticancer compounds tabulated in this study could be used as a template for further design and synthesis of promising congeneric synthetic compounds against another disease by the application of in silico high throughput screening through drug repositioning.