Analogues of vitamin E epitomised by alpha-tochopherol succinate (alpha-TOS) for pancreatic cancer treatment: in vitro results induce caution for in vivo applications

Context "Mitocans" destabilise mitochondria, causing apoptogenic factors\u2019 release. "Mitocans" include alpha-TOS, thought to be toxic only for cancer cells. Aims 1) To verify alpha-TOS effects on pancreatic cancer (PC) and normal cell growth; 2) to ascertain whether the combination of non toxic alpha-TOS and 5-FU dosages causes cancer cell death; 3) to obtain insights into caspase3 activation. Methods Five PC cell lines and normal monocytes were cultured in 1% and 10% FCS, without or with alpha-TOS (5, 10, 20, 50, 100, 200 and 500 \ub5M), for three days. Two cell lines were treated with 5-FU (0.0001 mM) and alpha-TOS (20 and 50 \ub5M) alone or in combination. Cell growth (XTT) and caspase3 activity (colorimetric method) were measured. Results In 1% FCS, 20 \ub5M or more alpha-TOS inhibited PC cell growth (F=57.9, P<0.001, BxPC3; F=91.8, P<0.001, Capan1; F=54.4, P<0.001, MIAPaCa2; F=48.9, P<0.001, Panc1; F=110.6, P<0.001, PSN1). In 10% FCS the same effect was obtained with higher alpha-TOS dosages (100, 200 and 500 \ub5M). Alpha-TOS dose dependently inhibited monocytes\u2019 growth in 1% FCS (F=110.5, P<0.001); 100 \ub5M or more were effective in 10% FCS (F=83.8, P<0.001). PSN1 growth (F=658, P<0.001), not Capan1 (F=63, P