Insights into the Role of Defective Apoptosis in Cancer Pathogenesis and Therapy

Abstract

One form of programmed cell death (PCD) is apoptosis. Defective apoptosis is an indispensable causative factor in the development of cancer that allows cancer cells to survive longer and favors the accumulation of oncogenic mutations. Further, upregulation of antiapoptotic proteins (e.g., Bcl-2, Mcl-1) and loss of pro-apoptotic proteins (e.g., Bid, Bad, Bax, Bak) strongly favors apoptosis evasion. The ability of cancer cells to evade apoptosis is critical for the progression and clonal expansion of malignantly transformed cells. Defective apoptosis imparts proliferative advantage to cancer cells or cells with the potential to become cancerous. The mechanisms employed by cancer cells to evade apoptosis can be used in the strategic design of therapeutic regimens aimed at exploiting apoptotic signaling networks to ensure tumor-specific cell death. Therefore, to ensure tumor-specific cell death, we may need to exploit the expression and/or function of different components of apoptotic signaling that are critical for maintaining cell survival and are regulated differently in tumor cells than normal cells. Both inhibitors of anti-apoptotic proteins and activators of pro-apoptotic proteins can be used for cancer therapy. In this chapter, we attempted to summarize the knowledge about the molecular mechanisms of defective apoptosis that could be translated into the development of novel therapeutic agents and therapeutic modalities for cancer treatment.

Knockdown of microRNA-375 suppresses cell proliferation and promotes apoptosis in human breast cancer cells

“…Interestingly, avoiding apoptosis is a critical process for transformed cancerous cells (47) . Control of cancer-related oncogenic miRNA expressions through synthetic miR-375 inhibitor is anticipated to play a role in developing new therapeutic intervention in cancer treatment (48) . Generally, cells commit to die due to their own pro-anti apoptotic proteins in apoptosis there by, it is generally referred to as a cell suicidal process and the balance between oncoproteins and tumour suppressor proteins are more responsible to determine when the cells die.…”

Germicidal and Antineoplastic Activities of Curcumin and Curcumin-Derived Nanoparticles

“…As a form of cell death, apoptosis is a highly regulated physiological process, which removes not only damaged, mutated, aged, and unrepairable cells, but also preserves the integrity and health of the entire organism. Apoptosis imbalances, either excessive or insufficient, may contribute to a variety of diseases including cancer [89,90]. As a cancer cell growth inhibitor, curcumin modulates multiple cellular signaling pathways such as those that induce apoptosis in several cancers including breast [91], malignant pleural mesothelioma [92], gastric cancer [93], acute lymphoblastic leukemia [94], lung cancer [95], pancreatic cancer [96] and gallbladder carcinoma [97].…”

The secretory scales and medicinal properties of combretum erythrophyllum.

“…In ailments such as cancer (uncontrolled cell growth), mediators are required to eliminate the cancer cells while exhibiting slight impact on normal cells, as research indicates high cellular resistance seen against conventional treatments i.e. chemotherapy (Thapa et al, 2021). This may be naturally induced through apoptosis, which may be lacking (cancer) or over expressed (neurodegenerative diseases) in certain ailments.…”