Tu1975 H2S Inhibition of Cystathionine-β-Synthase (CBS) Using Novel Prodrug Decreases Colorectal Cancer Xenograft Growth With Less Toxicity Than Aminooxyacetic Acid (AOAA)

Abstract

G A A b st ra ct s enhanced MEK/ERK activation coincided with those that inhibited mTORC2-mediated Akt phosphorylation on Ser473, suggesting a role of mTORC2. Knockdown of Rictor markedly increased baseline levels of ERK phosphorylation and treatment with NVP-BEZ235 did not produce further enhancement of ERK activation. These results imply that Rictor or mTORC2 exerts feedback inhibition of the MEK/ERK pathway in pancreatic cancer cells. Conclusion: We propose that dual PI3K/mTOR inhibitors suppress a novel negative feedback loop mediated by mTORC2 thereby leading to enhanced MEK/ERK pathway activity in pancreatic cancer cells.