Bufotalin is a steroid lactone isolated from Venenum Bufonis with potently antitumor activities, a selective and potent inhibitor of COL1A1-high NSCLC.
Bufotalin shows inhibitory effect on the viability of doxorubicin-induced multidrug resistant liver cancer cells (R-HepG2) than that of their parent cells HepG2.
Bufotalin induces cell cycle arrest at G(2)/M phase through down-regulation of Aurora A, CDC25, CDK1, cyclin A and cyclin B1, as well as up-regulation of p53 and p21.
Bufotalin significantly inhibited the growth of xenografted R-HepG2 cells.
Bufotalin physically engages COL1A1, triggering its post-transcriptional down-regulation and concomitantly crippling malignant fitness.
Bufotalin simultaneously disables the PTEN/AKT/mTOR and Ras/MEK/ERK cascades, enforces G2-M arrest via Cyclin B1/CDK1 dysregulation, and quells epithelial-to-mesenchymal transition by restoring E-cadherin while repressing N-cadherin, MMP3, and MMP9.