Caspase-inducing effects of lycorane and crinane alkaloids of the Amaryllidaceae

Cancer is a leading cause of death worldwide. This, in spite of the tremendous gains made in cancer chemotherapies over the past several decades. The identification and development of new targets with greater structural diversities and better potencies are at the forefront of drug discovery endeavors across disciplines. Plants have afforded a significant number of successful anticancer drugs, several of which manifest their activities by inducing apoptosis (or programmed cell death) in cancer cells. The Amaryllidaceae alkaloids have similarly distinguished themselves as potent antiproliferative agents, some at the nanomolar level, with selective apoptosis inducing effects demonstrated in a wide variety of cancer cells. The proteolytic enzymes caspases are the key effectors of the apoptotic pathways, the main function of which is, in turn, the activation of caspases. Once activated caspases set in motion an intricately choreographed cascade of events leading to eventual cell death and phagocytosis. The lycorane and crinane group of alkaloids were amongst the first of the Amaryllidaceae for which apoptosis and attendant caspase inducing effects were discovered. These have been central in ongoing efforts to unravel the mechanistic basis to the cytotoxicity of these alkaloids. This review focuses on the various caspases which have been shown to be integral in apoptosis signaling pathways mediated by lycorane and crinane alkaloids.