Figure 7.

Summary of gensitein-induced cell death. (a) In UtLM cells, genistein's inhibitory and/or death effects were mostly through autophagy. It could be speculated that genistein may have blocked the intrinsic apoptotic pathway in UtLM cells by inducing increased expression of Bcl-2 leading to starvation and self-digestion (autophagy) and cell survival. As a late event, autophagy can cause caspase activation and DNA fragmentation (apoptosis). Alternatively, inhibition of proteins involved in autophagy or a depletion of resources (nutrients or organelles) of the cell can cause a switch from autophagy to necrosis, leading to cytotoxicity and the release of lactate dehydrogenase (LDH). (b) In UtSMC, genistein induced apoptosis by primarily stimulating the extrinsic apoptotic pathway, via Fas-L and its receptor Fas with activation of caspases and induction of apoptosis. Also, initially the Bcl-2: bak ratios in genistein-treated UtSMC were decreased at 72 h (early event) due to elevated expression of the proapoptotic mediator, bak; however, the Bcl-2: bak ratio was increased at 168 h (late event) by incremental expression of Bcl-2. These findings suggest that the intrinsic pathway may be playing a dual role in UtSMC after genistein treatment; in that, bak may be involved in inducing apoptosis as an early event, whereas, this effect is abrogated by increased expression of Bcl-2 as a late event, which may be a last attempt at induction of cell survival in genistein-treated UtSMC.