tehranolide and Neoplasms

Identifying cancer biomarkers is imperative, as upregulated genes offer a better microenvironment for the tumor; hence, targeted inhibition is preferred. The theme of our study is to predict molecular interactions between cancer biomarker proteins and selected natural compounds. We identified an overexpressed potential molecular target (AKT1) and computationally evaluated its inhibition by four dietary ligands (isoliquiritigenin, shogaol, tehranolide, and theophylline). The three-dimensional structures of protein and phytochemicals were retrieved from the RCSB PDB database (4EKL) and NCBI's PubChem, respectively. Rational structure-based docking studies were performed using AutoDock. Results were analyzed based primarily on the estimated free binding energy (kcal/mol), hydrogen bonds, and inhibition constant, Ki, to identify the most effective anti-cancer phytomolecule. Toxicity and drug-likeliness prediction were performed using OSIRIS and SwissADME. Amongst the four phytocompounds, tehranolide has better potential to suppress the expression of AKT1 and could be used for anti-cancer drug development, as inhibition of AKT1 is directly associated with the inhibition of growth, progression, and metastasis of the tumor. Docking analyses reveal that tehranolide has the most efficiency in inhibiting AKT1 and has the potential to be used for the therapeutic management of cancer. Natural compounds targeting cancer biomarkers offer less rejection, minimal toxicity, and fewer side effects.

Topics: Antineoplastic Agents; Biomarkers, Tumor; Humans; Molecular Docking Simulation; Neoplasms; Proto-Oncogene Proteins c-akt; Sesquiterpenes; Tumor Microenvironment

Tehranolide named as new type of a sesquiterpene lactone with an endoperoxide group which purified from Artemisia diffusa and having similar structure to Artemisinin. Tehranolide is hypothesized to possess effects akin to Artemisinin, which is active against cancer cells. In the present research we emphasized on the direct correlation between the tumor sizes, immune response; including cytokin network, T regulatory cells and Tehranolide intraperitoneally injected Tehranolide. In this study, Tehranolide was purified from Artemisia difussa. First we evaluated the effects of Tehranolide on cell growth inhibition (in vitro) by MTT assay and second investigated the immune responses, these include measuring tumor growth in the female Balb/c mice transplanted with spontaneous mouse mammary tumor and treated with Tehranolide, splenocyte proliferation detected by using the BrdU kit, measurement of cytokine profile by ELISA and analysis of T-lymphocytes subpopulation in spleen by Flow cytometry. Our results showed a significant (p<0.05) decrease in the tumor volume and the level of IL-4 in the animals treated with Tehranolide, compared to untreated group. In addition, a significant (p<0.05) increase in the lymphocytes proliferation and the level of IFN-gamma in the animals treated with Tehranolide in comparison with control group. Furthermore, we regulate the regulatory T cells in order to improve the outcome of cancer immunotherapy. The measurement of splenic CD4(+)CD25(+)Foxp3(+) T lymphocytes indicated that Tehranolide significantly (p<0.05) decreased the number of these lymphocytes. These findings show that the use of Tehranolide molecule represents a novel strategy with major suggestions for cancer therapy approaches.

Topics: Animals; CD4-Positive T-Lymphocytes; Cell Line; Cell Survival; Female; Forkhead Transcription Factors; Hypersensitivity, Delayed; Injections, Intraperitoneal; Interferon-gamma; Interleukin-2 Receptor alpha Subunit; Interleukin-4; Mice; Mice, Inbred BALB C; Molecular Structure; Neoplasm Transplantation; Neoplasms; Sesquiterpenes; Sheep; T-Lymphocytes, Regulatory