Laherradurin Inhibits Tumor Growth in an Azoxymethane/Dextran Sulfate Sodium Colorectal Cancer Model In Vivo.

Colorectal cancer (CRC) is the third most common neoplasia in the world. Its mortality rate is high due to the lack of specific and effective treatments, metastasis, and resistance to chemotherapy, among other factors. The natural products in cancer are a primary source of bioactive molecules. In this research, we evaluated the antitumor activity of an acetogenin (ACG), laherradurin (LH), isolated from the Mexican medicinal plant Annona macroprophyllata Donn.Sm. in a CRC murine model. The CRC was induced by azoxymethane-dextran sulfate sodium (AOM/DSS) in Balb/c mice and treated for 21 days with LH or cisplatin. This study shows for the first time the antitumor activity of LH in an AOM/DSS CRC model. The acetogenin diminished the number and size of tumors compared with cisplatin; the histologic studies revealed a recovery of the colon tissue, and the blood toxicity data pointed to less damage in animals treated with LH. The TUNEL assay indicated cell death by apoptosis, and the in vitro studies exhibited that LH inhibited cell migration in HCT116 cells. Our study provides strong evidence of a possible anticancer agent for CRC.

Investigation of the DNA Damage and Oxidative Effect Induced by Venlafaxine in Mouse Brain and Liver Cells.

Venlafaxine is an antidepressant used worldwide. Therefore, studies to confirm its safe use are mandatory. This report evaluated the drug DNA damage capacity in the brain and liver of ICR mice, and its oxidative effect on DNA, lipids, and proteins, as well as the amount of nitrites, also in the brain and liver. Determinations were made at 2, 6, 12, and 24 h post-treatment, excluding DNA oxidation that was observed at 2 h. The tested doses of venlafaxine were 5, 50, and 250 mg/kg. The results showed DNA damage in the brain with the two more elevated doses of venlafaxine at 2 and 6 h post-treatment and also at 12 h in the liver. The comet assay plus the FPG enzyme showed DNA damage in both organs with all doses. The two high doses increased lipoperoxidation in the two tissues from 6 to 12 h post-administration. Protein oxidation increased with the three doses, mainly from 2 to 12 h, and nitrite content was elevated only with the high dose in the liver. The drug was found to affect both tissues, although it was more pronounced in the liver. Interestingly, DNA oxidative damage was observed even with a dose that corresponds to the therapeutic range. The clinical relevance of these findings awaits further investigations.