• Investigation of the mechanism of selected natural compounds in breast cancer and endometrial(cancer) through the PI3K/AKT/mTOR signaling pathway by molecular docking
  • Hanieh Fahmideh,1,* Mitra Hassani,2
    1. Department of Faculty of Basic Sciences and Advanced Technologies in Biology, Islamic university of Iran , Tehran, Iran
    2. Department of Microbial Biotechnology, Faculty of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran


  • Introduction: Despite the advancement of numerous treatments in the field of cancer, cancer remains one of the main concerns of the medical community. On the other hand, some researchers have investigated natural treatments for cancer and have presented promising results. But there is a long distance from theory and hypothesis to reality. This study attempts to investigate the relationship between one of the main signaling pathways involved in the progression of breast cancer and endometriosis and natural treatments suggested in previous studies using the molecular docking method. PI3K/AKT/mTOR signaling pathway plays an important role in the process of cell cycle and plays a role in proliferation and survival. This signaling pathway is known as a resistance factor in breast and endometrial cancers, which makes tumors resistant to conventional treatments of malignancies. Therefore, inhibiting the PI3K/AKT/mTOR pathway has been the focus of researchers for the treatment of the mentioned malignancies. Natural products such as resveratrol, curcumin, epigallocatechin gallate (EGCG), capsaicin, and kaempferol, which are derived from plants and fruits, have been candidates for investigation of their effects on the signaling pathway of interest.
  • Methods: To determine the affinity of the ligand and each of the natural products, molecular docking was performed with Pyrx software. The 3D structures of the ligands were obtained from the PDB database. The information and 2D and 3D structures of natural products have been extracted from PubChem database. The atoms participating in the interaction between the ligand and the protein were investigated using liGplot+ software.
  • Results: Resveratrol showed a binding energy of -7.5 kcal/mol for PI 3K. While curcumin was bound to PI 3K with a binding energy of -7.1 kcal/mol. EGCG showed the lowest binding energy among other natural products and was bound with -6.1 kcal/mol. Capsaicin bound to PI 3K with a binding energy of -6.2 kcal/mol. Among all investigated natural products, kaempferol has the highest binding affinity with the ligand and binds to the ligand with a binding energy of -7.8 kcal/mol. Resveratrol was bound to AKT protein with a lower binding energy than PI 3K, which was -7.2 kcal/mol. The binding energy of curcumin to this ligand was -8.1 kcal/mol. In the binding of natural products to this ligand, EGCG has shown the highest binding energy and has connected with the ligand with binding energy of -8.4 kcal/mol. And capsaicin has the lowest binding energy with the ligand with -6.9 kcal/mol. Kaempferol is also bound to AKT protein with a binding energy of -8.3 kcal/mol.
  • Conclusion: The key findings of this study show that, according to the bioinformatic information obtained from this study, natural compounds have the ability to influence the signaling pathways that control cancer. However, considering the physiological differences of each person's body and considering the pharmacodynamics and pharmacokinetics of each drug, as well as the influence of environmental and genetic factors on the course of the disease, natural compounds cannot be definitively considered as a replacement for conventional cancer treatment methods (surgery, radiotherapy, chemotherapy). To obtain more advanced results, all these findings should be examined more closely and further studies should be conducted in vitro and in vivo. Determining optimal doses, drug toxicity, investigating possible side effects, and animal testing can be valuable for advancing this study.
  • Keywords: Breast cancer , natural products , PI3K/AKT/mTOR signaling pathway , molecular docking