Induction of quinone reductase by withanolides.
Misico RI, Song LL, Veleiro AS, Cirigliano AM, Tettamanzi MC, Burton G, Bonetto GM, Nicotra VE, Silva GL, Gil RR, Oberti JC, Kinghorn AD, Pezzuto JM.
Thirty-seven naturally occurring withanolides (1-37), previously isolated in our laboratories, were evaluated for their potential to induce quinone reductase with cultured murine hepatoma cells (Hepa 1c1c7). Spiranoid (29, 32) and 18-functionalized withanolides (2-5, 7-9, 24) were found to be potent inducers of the enzyme, while 5alpha-substituted derivatives exhibited weak activity. Preliminary studies were performed with compound 29 to evaluate enzyme-inducing capacity in multiple organ sites of BALB/c mice. Significant induction was observed in liver and colon, but not in lung, stomach, or mammary gland.