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A Mini Review on Molecules Inducing Caspase-Independent Cell Death: A New Route to Cancer Therapy
1Department of Zoology, University of Kalyani, Nadia, Kalyani 741235, India.
Abstract:
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.
Insights
Targeting alternative cell death pathways offers a potent strategy against cancer, bypassing apoptosis inhibitors. Novel small molecules and natural compounds show promise for effective cancer treatment and prevention.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Most anticancer drugs induce apoptosis (programmed cell death) via caspase activation.
- Apoptosis can be inhibited by proteins like survivin and Hsp70, limiting drug efficacy.
- Mutations in caspase-dependent pathways reduce the potency of conventional anticancer therapies.
Purpose of the Study:
- To review anti-cancer drug molecules targeting alternative, caspase-independent cell death pathways.
- To provide a molecular basis for novel anti-cancer treatment strategies.
- To explore the potential of targeting alternative cell death mechanisms for cancer therapy.
Main Methods:
- Literature review of studies on small molecules targeting alternative cell death pathways.
- Analysis of natural compounds, inorganic compounds, synthetic molecules, and repurposed drugs.
- Examination of mechanisms causing caspase-dependent and caspase-independent cell death.
Main Results:
- Alternative cell death pathways offer potent therapeutic targets, circumventing apoptosis resistance.
- Numerous compounds, including natural products and repurposed drugs, induce caspase-independent cancer cell death.
- Some molecules exhibit dual activity, inducing both caspase-dependent and caspase-independent death in specific cancer types.
Conclusions:
- Targeting caspase-independent cell death pathways is a promising strategy for novel anticancer drug development.
- Small molecules inducing alternative cell death are valuable leads for rational therapeutic design.
- These approaches hold potential for future cancer prevention strategies.
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