The role of apoptosis in cancer cell survival and therapeutic outcome

Abstract

A number of discoveries have clarified the molecular mechanism of apoptosis, thus clarifying the link between apoptosis and therapeutic outcome. Even though apoptosis is thought to play a major role in anticancer therapy, the clinical relevance of induction of apoptosis remains uncertain, particularly in solid tumors. Induction of apoptosis by anticancer agents has been shown to correlate with tumor response, however, non-apoptotic forms of cell death, such as autophagy and extrinsic senescence, have also been shown to contribute to the overall tumor response. Cellular damage induces growth arrest and tumor suppression by inducing apoptosis, necrosis, and senescence; the mechanism of cell death depends on the magnitude of DNA damage following exposure to various concentrations of anticancer agents. Apoptosis-resistant cells and transduction pathways which inhibit apoptosis can induce non-apoptotic mechanisms of cell death and senescence, thereby preserving the antitumor effect of some anticancer agents. Heterogeneic antitumor responses include various cell types of cell death, depending on the degree of cellular or DNA damage incurred by cancer cells. As a new therapeutic strategy, alternative types of cell death might be exploited to control and eradicate cancer cells. This review discusses the clinical significance of apoptosis, as well as the potential contribution of other types of cell death to overall tumor sensitivity in the hopes that new therapeutic strategies might follow.

Monitoring of tumor response to chemotherapy in vivo by a novel small-molecule detector of apoptosis

“…The capability of ML-9 to detect or distinguish between these forms of cell death in vivo still remains to be elucidated in further studies. However, it is currently increasingly appreciated, that in vivo, transitional forms of cell death can be identified, with cells manifesting combined features of various forms of cell death processes [40][41][42][43]. Induction of apoptosis by chemotherapy in our study was verified by several distinct hallmarks of the death process, which were also found to correlate with a respective increased uptake of ML-9.…”

The dissociation of the Hsp60/pro-Caspase-3 complex by bis(pyridyl)oxadiazole copper complex ( CubipyOXA ) leads to cell death in NCI-H292 cancer cells

“…Apoptosis contributes to tumor demise following chemotherapy but, in patient management, it is still unclear how to achieve a healthy balance between cell proliferation and death [32]. In some instances, elevated levels of Hsps protect tumor cells against therapy-induced apoptosis [33].…”

Enhancement of ionizing radiation response by histamine in vitro and in vivo in human breast cancer

“…4,24 Furthermore, there is a large body of experimental evidence showing that a rise in the intracellular ROS contributes to cell senescence and may influence the overall tumor response to anticancer therapy. 25,26 The net intracellular concentration of ROS is the result of their production and the ability of antioxidants to remove them. Therefore, in order to investigate whether histamineinduced increase in cell apoptosis and senescence was associated with a modulation of ROS levels, we further examined ROS levels and the activity of some metabolizing antioxidant enzymes.…”