A Higher Frequency Administration of the Nontoxic Cycloartane-Type Triterpene Argentatin A Improved Its Anti-Tumor Activity.

Parthenium argentatum (Gray), commonly known as guayule, has been used to obtain natural rubber since the beginning of the 20th century. Additionally, the so called "resin" is a waste product derived from the industrial process. The cycloartane-type triterpene Argentatin A (AA) is one of the main constituents of the industrial waste resin. In this study we evaluated the AA anticancer activity both in vitro and in vivo in the HCT116 colon cancer cells. The apoptosis promotion of AA was assessed by the annexin V/propidium iodide (PI) assay. The senescence was evaluated for SA-ß-galactosidase, and PCNA was used as a marker of proliferation. Its antitumor activity was evaluated using a xenograft mouse model. The results indicated that AA-induced apoptosis in HCT-116 cells and was positively stained for SA-ß-galactosidase. In the xenografted mice test, the administration of AA at the dose of 250 mg/kg three times a week for 21 days reduced tumor growth by 78.1%. A comparable tumor reduction was achieved with cisplatin at the dose of 2 mg/kg administered three times a week for 21 days. However, nude mice treated with AA did not lose weight, as they did remarkably when treated with cisplatin. Furthermore, the animals treated with AA showed similar blood profiles as the healthy control group. These data indicate the low toxicity of AA compared to that shown by cisplatin.

The Phytosterol Peniocerol Inhibits Cell Proliferation and Tumor Growth in a Colon Cancer Xenograft Model.

Objective: This study aimed to evaluate the cytotoxic activity of peniocerol against human colon cancer cell lines and its antitumor effect in vivo in a xenograft model using nu/nu mice. Materials and Methods: SW-620, HCT-15, and HCT-116 colon cancer cell lines were treated with peniocerol for cytotoxicity by crystal violet technique. Cell apoptosis induction was detected by flow cytometry, and the antitumor activity of peniocerol was evaluated in a xenograft model of HCT-116 in nu/nu mice. After treatment, the effect of peniocerol was analyzed in histological sections of tumors by immunohistochemistry using DAPI, anti-PCNA, and PARP-1 antibodies. Results: Peniocerol inhibited cell growth and induced apoptosis in vitro in a time and dose-dependent manner. Besides, peniocerol administration (30 or 15 mg/kg) inhibited tumor growth and induced apoptosis in the xenograft mice. The lack of peniocerol toxicity was proved by a biochemical blood analysis of healthy nu/nu mice administrated with this sterol. Conclusions: Our results proved that peniocerol induces apoptosis in vitro and in vivo assays.