Rapid induction of apoptosis in human C33A cervical carcinoma cells by the synthetic retinoid 6-[3-(1-adamantyl)hydroxyphenyl]-2-naphtalene carboxylic acid (CD437)

First described by Kerr et al. (1972), apoptosis is a physiological form of cell death by active regulatory processes of eliminating cells for homeostatic regulation of tissue mass as a counterbalance to cell division during development and cellular immune responses (Thompson, 1995).Dysregulation of apoptosis may lead to altered cell number within the tissue and, finally, to malignant transformation.The process of apoptosis, which is manifested by cell shrinkage, chromatin condensation, nuclear segmentation and internucleosomal degradation of DNA (Kerr et al., 1972), is initiated in response to a variety of external and intracellular signals (Williams and Smith, 1993;Thompson, 1995), including treatment with certain retinoids (Lotan, 1995).Because retinoids, which induce apoptosis of malignant tumor cells, may be useful agents for cancer chemoprevention and therapy (Lotan, 1995), we investigated and reported on the ability of 4HPR to induce apoptosis in human cervical and head and neck carcinomas (Oridate et al., 1995(Oridate et al., , 1996b)).A report, which revealed that CD437 induces apoptosis in 2 human breast carcinoma cell lines (Shao et al., 1995), prompted us to examine the effect of this novel retinoid on human C33A cervical carcinoma cells.Here, we report on the ability of CD437 to induce rapidly apoptosis of C33A cells by a unique mechanism that appears to be independent of modulation of Bcl-2, Bcl-x, Bax, p53 and p21 (WAF1/CIP1).