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.

Use of STAT6 Phosphorylation Inhibitor and Trimethylglycine as New Adjuvant Therapies for 5-Fluorouracil in Colitis-Associated Tumorigenesis.

Colorectal cancer (CRC) is one of the most widespread and deadly types of neoplasia around the world, where the inflammatory microenvironment has critical importance in the process of tumor growth, metastasis, and drug resistance. Despite its limited effectiveness, 5-fluorouracil (5-FU) is the main drug utilized for CRC treatment. The combination of 5-FU with other agents modestly increases its effectiveness in patients. Here, we evaluated the anti-inflammatory Trimethylglycine and the Signal transducer and activator of transcription (STAT6) inhibitor AS1517499, as possible adjuvants to 5-FU in already established cancers, using a model of colitis-associated colon cancer (CAC). We found that these adjuvant therapies induced a remarkable reduction of tumor growth when administrated together with 5-FU, correlating with a reduction in STAT6-phosphorylation. This reduction upgraded the effect of 5-FU by increasing both levels of apoptosis and markers of cell adhesion such as E-cadherin, whereas decreased epithelial-mesenchymal transition markers were associated with aggressive phenotypes and drug resistance, such as ß-catenin nuclear translocation and Zinc finger protein SNAI1 (SNAI1). Additionally, Il-10, Tgf-ß, and Il-17a, critical pro-tumorigenic cytokines, were downmodulated in the colon by these adjuvant therapies. In vitro assays on human colon cancer cells showed that Trimethylglycine also reduced STAT6-phosphorylation. Our study is relatively unique in focusing on the effects of the combined administration of AS1517499 and Trimethylglycine together with 5-FU on already established CAC which synergizes to markedly reduce the colon tumor load. Together, these data point to STAT6 as a valuable target for adjuvant therapy in colon cancer.

miRNA profile obtained by next­generation sequencing in metastatic breast cancer patients is able to predict the response to systemic treatments.

Metastatic breast cancer (MBC) is a challenge for oncologists, and public efforts should focus on identifying additional molecular markers and therapeutic management to improve clinical outcomes. Among all diagnosed cases of breast cancer (BC; approximately 10%) involve metastatic disease; notably, approximately 40% of patients with early­stage BC develop metastasis within 5 years. The management of MBC consists of systemic therapy. Despite different treatment options, the 5­year survival rate is <20%, which may be due to a lack of response with de novo or acquired resistance. MicroRNAs (miRNAs or miRs) are promising biomarkers as they are readily detectable and have a broad spectrum and potential clinical applications. The aim of this study was to identify a miRNA profile for distinguishing patients with MBC who respond to systemic treatment. Patients with MBC were treated according to the National Comprehensive Cancer Network guidelines. We performed miRNA­Seq on 9 primary tumors using the Thermo Fisher Scientific Ion S5 system. To obtain global miRNA profiles, we carried out differentially expressed gene elimination strategy (DEGES) analysis between the responsive and non­responsive patients. The results identified a profile of 12 miRNAs associated with the response to systemic treatment. The data were validated in an independent cohort (TCGA database). Based on the results, the upregulation of miR­342­3p and miR­187­3p was associated with the response to systemic treatment, and with an increased progression­free survival (PFS) and overall survival (OS); by contrast, the downregulation of miR­301a­3p was associated with a higher PFS and OS. On the whole, the findings of this study indicate that these miRNAs may serve as biomarkers for the response to systemic treatment or the prognosis of patients with MBC. However, these data should be validated experimentally in other robust cohorts and using different specimens before implementing these miRNAs as biomarkers in clinical practice to benefit this group of patients.

Selective Acetogenins and Their Potential as Anticancer Agents.

The Kingdom Plantae has provided several successful drugs for the treatment of different diseases, including cancer, and continues to be a source of new possible therapeutic molecules. For example, the annonaceous acetogenins (AAs) are secondary metabolites found in the Annonaceae family, which are plants employed in traditional medicine for the treatment of cancer and various other diseases. These polyketides are inhibitors of Complex I in the respiratory chain of tumor cells, a process that is closely related to tumor metabolism, cell death, apoptosis, and autophagy. The goal of this review is to update readers on the role of the AAs as antitumor agents using in vitro and in vivo studies to demonstrate their importance in the area of oncology drug discovery. For this purpose, we performed a literature search in the PubMed scientific database using a range of keywords, including acetogenins and cancer, acetogenins antitumor activity, acetogenins and cytotoxicity, and acetogenins mechanism of action, among others. As a result, we found that the AAs are cytotoxic compounds that can induce apoptosis, cell cycle arrest, and autophagy in vitro, in addition to exhibiting tumor growth inhibition in vivo. The functional group related to their antineoplastic activity is suggested to be the mono or bis tetrahydrofuran ring accompanied by two or more hydroxy groups. The versatility of the AA bioactivity therefore renders them potential therapeutic agents for cancer treatment. It is therefore apparent that nature is worth further examination to aid in the discovery of more effective, accurate, and less harmful therapies in the fight against cancer.

Transcriptomic Profiling of Adipose Tissue in Obese Women in Response to Acupuncture Catgut Embedding Therapy with Moxibustion.

OBJECTIVE: Complementary and alternative medicine, such as Traditional Chinese Medicine, represents an efficient therapeutic option for obesity control. It was previously reported that acupuncture catgut embedding therapy (ACET) with moxibustion reduces body weight and reverts insulin resistance in obese women. This study aimed to evidence changes in adipokines and gene expression in adipose tissue that could explain the effects of ACET with moxibustion. DESIGN: Overweight/obese women were treated with ACET with moxibustion or sham acupuncture as control. Peripheral blood samples and fat biopsies were taken before and after intervention. Circulating adipokines (leptin, adiponectin, tumor necrosis factor alpha, and resistin) were quantified by enzyme-linked immunosorbent assay. Gene expression in adipose tissue was determined by cDNA microarray assays and assessed by quantitative reverse transcription real-time polymerase chain reaction. RESULTS: ACET with moxibustion did not modify circulating adipokines levels. However, correlations with anthropometric and biochemical parameters were affected. Interestingly, transcriptional changes in adipose tissue revealed the modulation of genes participating in homeostasis control, lipid metabolism, olfactory transduction, and gamma-aminobutyric acid signaling pathway. CONCLUSIONS: The effects of ACET with moxibustion on body weight and insulin resistance were associated with the regulation of biochemical events that are altered in obesity.

Medicinal plants used in Mexican traditional medicine for the treatment of colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Cancer cases numbers are increasing worldwide positioning this disease as the second cause of mortality for both sexes. Medicinal plants have been used in the fight against cancer as the basis for drug discovery and nowadays more than 70% of anticancer drugs have a natural origin. Mexico is regarded for its cultural and biological diversity, which is reflected in the vast traditional knowledge of herbal remedies. In this review we examined herbal remedies employed in colorectal cancer treatment (CRC). AIM OF THE STUDY: The goal of this work was to gather scientific reports of plants used in Mexican traditional medicine for CRC treatment. MATERIALS AND METHODS: We performed a search on scientific literature databases using as keywords: "colon cancer", "gastric cancer", "cytotoxicity", studies "in vitro and in vivo", in combination with "Mexican medicinal plants" or "Mexican herbal remedies". The selection criteria of cytotoxic activity for extracts or pure compounds was based on the National Cancer Institute of USA recommendations of effective dose 50 (ED50) of ≤20µg/mL and ≤4µg/mL, respectively. RESULTS: In this review we report 25 botanic families and 39 species of plants used for the treatment of colon cancer in Mexico with evidence in studies in vitro and in vivo. CONCLUSIONS: Medicinal plants are still a great source of novel chemical structures with antineoplastic potential as it is proven in this work. The selection criteria and activity was narrowed for methodological purposes, nevertheless, drug discovery of natural origin continues to be a highly attractive R&D strategy.