ent-11alpha-Hydroxy-15-oxokaur-16-en-19-oic acid

Ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid induces apoptosis of human malignant cancer cells.[Pubmed:23140284]

Curr Drug Targets. 2012 Dec;13(14):1730-7.

Ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F) is a chemical compound isolated from Pteris semipinnata L (PsL), a Chinese traditional herb. 5F has been known to exert antitumor activity in several kinds of human malignant cancer cells by leading cancer cell to apoptosis. 5F translocated Bax into the mitochondria, down-regulated Bcl-2, activated caspase-9 and caspase-3, released cytochrome c into the cytosol and translocated AIF from the mitochondria to the nucleus. The presentation of a wild-type p53 in the cancer cells facilitated cancer cells sensitive to the 5F treatment. 5F induces apoptosis of cancer cells by inhibiting NF-kappaB activation/induction, which leading to the decrease of Bcl-2 but the increase of Bax and Bak. MAPK kinases and Akt are also involved in process of 5F inducing cancer cell apoptosis. In lung cancer, 5F activated ERK1/2 and the inhibition of ERK1/2 suppressed 5F-mediated changes in apoptotic molecules. 5F activated Akt and suggested that Akt activation was anti-apoptotic rather than pro-apoptotic. However, in anaplastic thyroid carcinoma, JNK activation was related to cell death induced by 5F. ERK and p38 were also activated but as survival signals in response to 5F treatment to counteract the induction of cell death. Collectively, 5F is effective against several malignant cancers both in vivo and in vitro with minimal side effects. It induces apoptosis through the mitochondrialmediated pathway, in which regulation of Bcl-2 family proteins expression, the activation of MAPK and inactivation of NF-kappaB are critical. The good ability of 5F to inhibit cancer cells makes it in line with the successful development of other anti-tumor agents.

Ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid inhibits hepatocellular carcinoma in vitro and in vivo via stabilizing IkBalpha.[Pubmed:22227815]

Invest New Drugs. 2012 Dec;30(6):2210-8.

Ent-11-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F) isolated from Pteris Semipinnata L is known to inhibit certain tumor cells in vitro. The information on the in vivo effect of 5F is limited and its effect on hepatocellular carcinoma (HCC) is unknown. In this study, the anti-tumor effect of 5F was investigated in a diethylnitrosamine (DEN)-induced mouse HCC model. In addition to therapeutic effect, the potential side effect was monitored. A panel of cultured HCC cells was used to confirm the in vivo data and explore the responsible molecular pathway. The result showed that 5F significantly inhibited the DEN-induced HCC tumors by reducing the number of tumor foci and the volume of tumors. Furthermore, 5F induced the death of cultured HCC cells in dose- and time-dependent manners. The cell death was confirmed to be apoptotic by in vivo and in vitro TUNEL assays. 5F inhibited NF-kB by stabilizing its inhibitor IkBalpha, reducing the nuclear p65 and inhibiting NF-kB activity. Subsequently it affected the NF-kB downstream molecules with a decrease in anti-apoptotic Bcl-2 and increase in pro-apoptotic Bax and Bak. During the whole period of the experiment, mice receiving 5F appeared to be healthy, though they suffered from a mild degree of hair loss. 5F did not damage liver and renal functions. In conclusion, 5F is effective against HCC with minimal side effects. It induces apoptosis in HCC cells via inhibiting NF-kB, leading to the decrease of Bcl-2 but the increase of Bax and Bak.