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.

Evaluations of Anticancer Effects of Combinations of Cisplatin and Tirucallane-Type Triterpenes Isolated from Amphipterygium adstringens (Schltdl).

The cytotoxic activity of combinations of masticadienonic (AMD) or 3αOH-hydroxy-masticadienonic (3αOH-AMD) acids with cisplatin (CDDP) was evaluated against PC3 prostate and HCT116 colon cancer cell lines. Combinations A (half the IC50 value), B (IC50 value), and C (twice the IC50 value) were tested at a 1 : 1 ratio. All AMD plus CDDP combinations demonstrated increased cytotoxic effect, as determined by the sulforhodamine B test, in both cell types. The best combination was B, which showed 93 % and 91 % inhibition of the proliferation of PC3 and HCT116 cells, respectively. It also increased apoptosis in the PC3 cell lines, as evaluated by flow cytometry. However, in vivo tests showed no additional activity from the AMD plus CDDP combinations. These results showed that the increased cytotoxic activity of the combinations in vitro did not reflect in vivo tests. All combinations of 3αOH-AMD plus CDDP exerted antagonistic effects in both cell types.

A triple-drug combination induces apoptosis in cervical cancer-derived cell lines.

Introduction: Cervical cancer is a worldwide health problem due to the number of deaths caused by this neoplasm. In particular, in 2020, 30,000 deaths of this type of tumor were reported in Latin America. Treatments used to manage patients diagnosed in the early stages have excellent results as measured by different clinical outcomes. Existing first-line treatments are not enough to avoid cancer recurrence, progression, or metastasis in locally advanced and advanced stages. Therefore, there is a need to continue with the proposal of new therapies. Drug repositioning is a strategy to explore known medicines as treatments for other diseases. In this scenario, drugs used in other pathologies that have antitumor activity, such as metformin and sodium oxamate, are analyzed. Methods: In this research, we combined the drugs metformin and sodium oxamate with doxorubicin (named triple therapy or TT) based on their mechanism of action and previous investigation of our group against three CC cell lines. Results: Through flow cytometry, Western blot, and protein microarray experiments, we found TT-induced apoptosis on HeLa, CaSki, and SiHa through the caspase 3 intrinsic pathway, including the critical proapoptotic proteins BAD, BAX, cytochrome-C, and p21. In addition, mTOR and S6K phosphorylated proteins were inhibited in the three cell lines. Also, we show an anti-migratory activity of the TT, suggesting other targets of the drug combination in the late CC stages. Discussion: These results, together with our former studies, conclude that TT inhibits the mTOR pathway leading to cell death by apoptosis. Our work provides new evidence of TT against cervical cancer as a promising antineoplastic therapy.

HPV-Based Screening, Triage, Treatment, and Followup Strategies in the Management of Cervical Intraepithelial Neoplasia.

Cervical cancer is the second most common cause of death from cancer in women worldwide, and the development of new diagnostic, prognostic, and treatment strategies merits special attention. Many efforts have been made to design new drugs and develop immunotherapy and gene therapy strategies to treat cervical cancer. HPV genotyping has potentially valuable applications in triage of low-grade abnormal cervical cytology, assessment of prognosis and followup of cervical intraepithelial neoplasia, and in treatment strategies for invasive cervical cancer. It is known that during the development of cervical cancer associated with HPV infection, a cascade of abnormal events is induced, including disruption of cellular cycle control, alteration of gene expression, and deregulation of microRNA expression. Thus, the identification and subsequent functional evaluation of host proteins associated with HPV E6 and E7 oncoproteins may provide useful information in understanding cervical carcinogenesis, identifying cervical cancer molecular markers, and developing specific targeting strategies against tumor cells. Therefore, in this paper, we discuss the main diagnostic methods, management strategies, and followup of HPV-associated cervical lesions and review clinical trials applying gene therapy strategies against the development of cervical cancer.