D. Yamamoto et al., Synergistic action of apoptosis induced by eicosapentaenoic acid and TNP-470 on human breast cancer cells, BREAST CANC, 55(2), 1999, pp. 149-160
The effects of eicosapentaenoic acid (EPA) and an angiogenesis inhibitor (T
NP-470) on the suppression of breast cancer cell growth were examined in fi
ve human breast cancer cell lines (MDA-MB-231, T-47D, MCF-7, KPL-1, and MKL
-F). In all five cell lines, EPA and TNP-470 alone both showed tumor growth
inhibition in a time- and dose-dependent manner, and in combination, a syn
ergistic effect was seen at high concentrations. EPA plus TNP-470 treatment
evoked apoptosis as confirmed by the appearance of sub G1 populations, by
DNA fragmentation, and by cell morphology. With the combination, the expres
sion of Bax and Bc1-x(S), the apoptosis-enhancing proteins, was more up-reg
ulated and that of Bcl-2 and Bcl-x(L), the apoptosis-suppressing proteins,
was more down-regulated compared to the use of EPA or TNP-470 alone, sugges
ting that their synergistic effect was due to an acceleration of apoptosis.