Apoptosis, or programmed cell death, is a crucial process in many biological functions. Several factors can increase its occurrence.
Factors that Increase Apoptosis
Many internal and external factors can trigger increased apoptosis. These include:
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Exposure to harmful substances: Anticancer drugs, gamma and ultraviolet irradiation are known initiators of apoptosis. These agents damage cellular components, triggering the cell's self-destruction mechanism. (Reference: Initiators of apoptosis include anticancer drugs, gamma and ultraviolet irradiation...)
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Withdrawal of survival factors: The absence of essential survival factors, such as interleukin-1 and other cytokines, can lead to an increase in apoptosis. Cells require these signals to stay alive; their absence signals the cell to undergo programmed death. (Reference: Initiators of apoptosis include... deprivation of survival factors such as interleukin-1...)
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Activation of death receptors: Certain cytokines activate "death receptors," such as Fas and tumor necrosis factor receptors, initiating the apoptotic cascade. This is a key mechanism in eliminating cells that are no longer needed or are harmful. (Reference: Initiators of apoptosis include... various other cytokines that activate “death receptors” such as Fas and tumour necrosis factor receptors.)
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Specific Disease States: Increased apoptosis is observed in several diseases. For instance, type 2 diabetes is associated with a significantly higher rate of β-cell apoptosis. (Reference: The frequency of β-cell apoptosis was increased 10-fold in lean and 3-fold in obese cases of type 2 diabetes compared with their...) Similarly, Huntington's disease is linked to increased apoptosis in lymphoblasts. (Reference: Increased apoptosis of Huntington disease lymphoblasts associated...)
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Genetic Factors: Genetic mutations, such as those leading to expanded CAG repeats in the huntingtin gene (Huntington's disease), can influence the rate of apoptosis. (Reference: Huntington disease (HD) is a genetically dominant condition caused by expanded CAG repeats coding for glutamine in the HD gene product huntingtin.) Similarly, knockout of myeloid cell leukemia-1 increases apoptosis susceptibility in murine hepatocytes. (Reference: Knockout of myeloid cell leukemia-1 induces liver damage and increases apoptosis susceptibility of murine hepatocytes.)
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Pharmaceutical Interventions: Certain drugs can increase apoptosis. For example, fluvastatin has been shown to reduce tumor proliferation and increase apoptosis in breast cancer cells. (Reference: Fluvastatin showed measurable biologic changes by reducing tumor proliferation and increasing apoptotic activity in high-grade, stage 0/1 breast cancer.) Conversely, heat shock protein 70 has been shown to inhibit apoptosis, suggesting that its inhibition might increase apoptosis. (Reference: Heat shock protein 70 increases tumorigenicity and inhibits... Pancreatic carcinoma is a malignant disease that responds poorly to chemotherapy because of its resistance to apoptosis.)
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Inhibition of certain pathways: Inhibition of pathways like PI3K/Akt and NF-kappaB, crucial for cell survival, can increase apoptosis. (Reference: EP4 deficiency inhibits the PI3K/Akt and NF-kappaB pathways compromising macrophage survival and suppressing early atherosclerosis.) Likewise, inhibition of histone deacetylase 2 increases apoptosis. (Reference: Inhibition of histone deacetylase 2 increases apoptosis and p21Cip1...)
Understanding the role of p53
The tumor suppressor protein p53 plays a critical role in inducing apoptosis. Its mechanisms are complex but essentially involve triggering a cascade of events leading to cell death. (Reference: In this review we discuss current understanding of the mechanisms by which p53 induces cell death and how this affects p53-mediated tumour suppression.)
