Comparison of cell deaths induced by transmembrane and secretory TNF-alpha.

Our previous study showed that transmembrane TNF-alpha (TM-TNF-alpha) had broader tumoricidal spectrum than secretory TNF-alpha (s-TNF-alpha). This study examined the difference between the two kinds of TNF-alpha in inducing cells and the relationship between the apoptosis induced by TM-TNF-alpha and the cell cycle. Bioassay was employed to compare the cytotoxic effect of two kinds of TNF-alpha on cell lines L-929 and HepG2. TUNEL was used to detect apoptosis and the TdT and PI co-staining were used for determining the phase of apoptotic cells. Our results showed that TM-TNF-alpha could kill not only s-TNF-sensitive L929 cells but also s-TNF-tolerant HepG2 cells. TM-TNF-alpha predominantly induced apoptosis while s-TNF could induce both apoptosis and necrosis. The apoptosis of L-929 cells induced by TM-TNF-alpha mainly occurred in S phase and the apoptosis of HepG2 predominantly took place in G(1) phase. It is concluded that the cytotoxic effects of the two TNF differ substantially. Since TM-TNF-alpha works locally, mainly induces apoptosis and has broader anti-tumor spectrum, it may be more effective for the treatment of tumor than s-TNF.