Fig. 6.

Paclitaxel induces synthesis of glutathione, which inhibits MEK1 activity, increases FoxO3 activity and pluripotency factor expression and promotes tumor initiation. (A–C), MDA-MB-231 subclones were implanted into SCID mice. When tumor volume reached 200 mm³ (day 0), mice were randomly assigned to treatment with i.p. injections of saline [Pac (-)] or 10 mg/kg paclitaxel [Pac (+)] on days 0, 5, and 10. Tumors were harvested on day 13, and samples were analyzed for intracellular total glutathione levels (A), percentage of ALDH (+) cells (B), and protein expression as indicated (C) (mean ± SEM; n = 3). *P < 0.05, **P < 0.01, ***P < 0.001 vs. NTC Pac (-); ^#P < 0.05, ^##P < 0.01, ^###P < 0.001 vs. NTC Pac (+); ns, not significant. (D) One thousand cells of each MDA-MB-231 subclone were implanted into the mammary fat pad of female SCID mice. The number of mice that developed palpable tumors after 65 d in each group was reported, and Fisher’s exact test was performed to determine statistical significance vs. NTC group.