20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol, a novel natural product for prostate cancer therapy: activity in vitro and in vivo and mechanisms of action

Abstract

We recently isolated 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol (25-OCH3-PPD), a natural product from Panax notoginseng, and demonstrated its cytotoxicity against a variety of cancer cells. Here we report the effects of this compound in vitro and in vivo on human prostate cancer cells, LNCaP (androgen-dependent) and PC3 (androgen-independent), in comparison with three structurally related ginsenosides, ginsenoside Rh2, ginsenoside Rg3, and 20(S)-protopanaxadiol. Of the four test compounds, 25-OCH3-PPD was most potent. It decreased survival, inhibited proliferation, induced apoptosis, and led to G1 cell cycle arrest in both cell lines. It also decreased the levels of proteins associated with cell proliferation (MDM2, E2F1, cyclin D1, and cdks 2 and 4) and increased or activated pro-apoptotic proteins (cleaved PARP, cleaved caspase-3, -8, and -9). In LNCaP cells, 25-OCH3-PPD inhibited the expression of the androgen receptor and prostate-specific antigen. Moreover, 25-OCH3-PPD inhibited the growth of prostate cancer xenograft tumours. Combining 25-OCH3-PPD with conventional chemotherapeutic agents or with radiation led to potent antitumour effects; tumour regression was almost complete following administration of 25-OCH3-PPD and either taxotere or gemcitabine. 25-OCH3-PPD also demonstrated low toxicity to noncancer cells and no observable toxicity in animals. In conclusion, our preclinical data indicate that 25-OCH3-PPD is a potential therapeutic agent against both androgen-dependent and androgen-independent prostate cancer.

Down-regulation of Phosphoglucose Isomerase/Autocrine Motility Factor Enhances Gensenoside Rh2 Pharmacological Action on Leukemia KG1α Cells

“…Ginseng extracts and its chemical components have been demonstrated their cytotoxicity against a variety of cancers, including inhibition of carcinogenesis in oral cavity, stomach, lung, liver, pancreas, ovaries, and colon (Wang et al, 2008). The ingredients of ginseng were complex, more than one hundreds of ginsenosides were found (Christensen., 2009).…”

Japonicone A Suppresses Growth of Burkitt Lymphoma Cells through Its Effect on NF-κB

“…Because of their rich structural diversity and promising therapeutic applications, natural products and their derivatives have caught the attention of pharmacologists and chemists (18,19). We have been interested in developing new, effective, and safe drugs from natural products for cancer therapy (25,(46)(47)(48). Inula japonica Thunb is a traditional medicinal herb used for treatment of bronchitis, digestive disorders, diabetes, and inflammation.…”

Self-microemulsifying drug-delivery system for improved oral bioavailability of 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol: preparation and evaluation

“…2 It also decreased levels of proteins associated with cell proliferation (MDM2, E2F1, cyclin D1, and cyclin-dependent kinases 2 and 4) and increased or activated proapoptotic proteins (cleaved poly ADP ribose polymerase, caspase-3, caspase-8, and caspase-9). 2 However, 25-OCH 3 -PPD had extremely low aqueous solubility, indicating low oral bioavailability. Low aqueous solubility is a common characteristic in biopharmaceuticals today, and according to some estimates, over 40% of new chemical entities show poor solubility, which is an obstacle to the use of new compounds.…”