7-methoxyheptaphylline

**7-methoxyheptaphylline** is a naturally occurring carbazole alkaloid isolated from the root bark of *Clausena harmandiana*, a medicinal plant traditionally used for treating headaches and stomachaches[3][4][5][7][9]. It is structurally related to heptaphylline, with a methoxy group substituted at the 7-position on the carbazole ring[2]. 7-methoxyheptaphylline exhibits selective cytotoxicity toward various cancer cell lines, including HT29 colon adenocarcinoma, PANC-1 pancreatic cancer, SH‑SY5Y neuroblastoma, HepG2 hepatocellular carcinoma, LNCaP prostate cancer, and 4T1 breast cancer cells, while showing minimal toxicity to normal cells[1][3][4][5][7]. Mechanistically, 7-methoxyheptaphylline: - Sensitizes death receptor-mediated (TRAIL) apoptosis in cancer cells by upregulating the TRAIL receptor DR5 via the JNK (c-Jun N-terminal kinase) pathway, leading to caspase-3 and caspase-8 activation and enhanced apoptotic cell death[1]. - Suppresses cancer metastasis in vitro and in vivo (anti-metastatic effect in pancreatic, breast and colon cancer models)[7][10]. - Inhibits PI3K/Akt/mTOR pathway signaling, notably under nutrient deprivation, reducing Akt and mTOR phosphorylation in pancreatic cancer models[7]. - Reduces survival and metastatic signaling (NF-κB, STAT3, Erk, MAPK13, matrix metalloproteinase-9)[3][4][5]. - Directly binds and occupies the ATP-binding site of TAK1 kinase (Transforming growth factor-beta-activated kinase 1), interfering with kinase activity, as shown by molecular docking studies[4]. Additionally, 7-methoxyheptaphylline has demonstrated neuroprotective properties against oxidative stress-induced neuronal cell death in vitro[3][4][5].

Other names

7-MH