The Case Against Apoptosis

Abstract

Apoptosis is not as dominant a process in cell loss from normal tissues and tumours as has sometimes been claimed. The term 'programmed cell death', which many authors regard as synonymous with apoptosis, is an unsatisfactory term that is best avoided. In studies on the response of tumours to drug and radiation treatment, the use of apoptosis assays concentrates attention on the first decade of cell killing (0-90%), whereas the outcome of treatment depends on multi-log cell kill; an assay of clonogenic cell survival is the appropriate method for this purpose. Loss of colony-forming ability is the key event in treated tumour cells, and the appearance of morphological and molecular evidence of apoptosis is probably downstream from this event. Published studies that have compared apoptosis and cell survival responses in tumour cells have generally failed to find a causal relationship.

Mitochondrial modulation of oxygen-dependent radiosensitivity in some human tumour cell lines

“…oxygen-dependent radiosensitivity of HeLa cells under our conditions is independent of both Bcl-2 and Bax, consistent with other reports that Bcl-2 proteins [28,29,36,37] and apoptosis [38][39][40] are not important determinants of radiosensitivity.…”

Tamoxifen-loaded solid lipid nanoparticles-induced apoptosis in breast cancer cell lines

“…[1,2] Other mode of cell death has also been suggested, for example mitotic cell death, which plays an important role in cell death caused by ionising radiation. [3] Breast cancer is the most common malignancy (18% of all malignancies) in women worldwide and its occurrence is slowly increasing. [4] Like many cancers, breast cancer appears to be a result of high genetic damage that caused uncontrolled cellular proliferation and unusual apoptosis.…”

Apoptosis assays with lymphoma cell lines: problems and pitfalls

“…In recent years, the idea that tumour cells treated with cytotoxic drugs or radiation die owing to apoptosis (programmed cell death), as opposed to the direct effect of the treatment itself, has become widely accepted (Barry et al, 1990;Reed et al, 1994;Aldridge and Radford, 1998;Ferreira et al, 2002;Jazirehi et al, 2003;Okada and Mak, 2004). There are, however, a few persuasive skeptics (Brown and Wouters, 1999;Steel, 2001;Gerl and Vaux, 2005). We have begun to investigate the mechanism of cell death induced by radiolabelled antibodies (Abs), primarily using radionuclides emitting low-energy electrons (some Auger and conversion electrons) (Griffiths et al, 1999;Ong et al, 2001).…”