Most anticancer treatments trigger tumor cell death through apoptosis, where initiation of proteolytic action of caspase protein is a basic need. But under certain circumstances, apoptosis is prevented by the apoptosis inhibitor proteins, survivin and Hsp70. Several drugs focusing on classical programmed death of the cell have been reported to have low anti-tumorogenic potency due to mutations in proteins involved in the caspase-dependent programmed cell death with intrinsic and extrinsic pathways. This review concentrates on the role of anti-cancer drug molecules targeting alternative pathways of cancer cell death for treatment, by providing a molecular basis for the new strategies of novel anti-cancer treatment. Under these conditions, active agents targeting alternative cell death pathways can be considered as potent chemotherapeutic drugs. Many natural compounds and other small molecules, such as inorganic and synthetic compounds, including several repurposing drugs, are reported to cause caspase-independent cell death in the system. However, few molecules indicated both caspase-dependent as well caspase-free cell death in specific cancer lines. Cancer cells have alternative methods of caspase-independent programmed cell death which are equally promising for being targeted by small molecules. These small molecules may be useful leads for rational therapeutic drug design, and can be of potential interest for future cancer-preventive strategies.
Keywords: apoptosis; apoptosis inducing factor AIF; caspase-dependent programmed cell death; caspase-independent programmed cell death.