Natural Products as Chemopreventive Agents by Potential Inhibition of the Kinase Domain in ErbB Receptors

Abstract

Small molecules found in natural products provide therapeutic benefits due to their pharmacological or biological activity, which may increase or decrease the expression of human epidermal growth factor receptor (HER), a promising target in the modification of signaling cascades involved in excessive cellular growth. In this study, in silico molecular protein-ligand docking protocols were performed with AutoDock Vina in order to evaluate the interaction of 800 natural compounds (NPs) from the NatProd Collection (), with four human HER family members: HER1 (PDB: 2ITW), HER2 (PDB: 3PP0), HER3 (PDB: 3LMG) and HER4 (PDB: 2R4B). The best binding affinity values (kcal/mol) for docking pairs were obtained for HER1-podototarin (−10.7), HER2-hecogenin acetate (−11.2), HER3-hesperidin (−11.5) and HER4-theaflavin (−10.7). The reliability of the theoretical calculations was evaluated employing published data on HER inhibition correlated with in silico binding calculations. IC50 values followed a significant linear relationship with the theoretical binding Affinity data for HER1 (R = 0.656, p < 0.0001) and HER2 (R = 0.543, p < 0.0001), but not for HER4 (R = 0.364, p > 0.05). In short, this methodology allowed the identification of several NPs as HER inhibitors, being useful in the discovery and design of more potent and selective anticancer drugs.

Experimental, molecular docking and molecular dynamic studies of natural products targeting overexpressed receptors in breast cancer

“…The various studies have proved that hesperidin has a capacity to induce cancer cell death including breast, lung, colon, liver, and gastric cancers [ 6 , 19 ]. Also, a study showed that the hesperidin significantly inhibits the colony formation of MCF7 cells [ 27 ].…”

“…A study has shown that the expression of this receptor significantly increases in breast cancer up to 80% of cells [ 5 ]. Also, the human epidermal growth factor receptor (HER) generates a cascade of responses able to advance the formation and progression of breast cancer [ 6 ]. Therefore, the activation of HER receptors leads to modification in the behavior of normal cells through the final signals for cellular proliferation, anti-apoptosis, angiogenesis, and metastasis [ 6 , 7 ].…”

“…Also, the human epidermal growth factor receptor (HER) generates a cascade of responses able to advance the formation and progression of breast cancer [ 6 ]. Therefore, the activation of HER receptors leads to modification in the behavior of normal cells through the final signals for cellular proliferation, anti-apoptosis, angiogenesis, and metastasis [ 6 , 7 ]. On the other hand, the ability of cancer cells to evade apoptosis is a crucial feature for them, so that they frequently dysregulate the intrinsic apoptotic pathway to preserve tumor cell survival through upregulation of anti-apoptotic Bcl-2 family proteins, including Bcl2-A1, Bcl-2, Bcl-xL, Bcl-w, and Mcl-1 [ 8 ].…”

“…The use of natural products in drug discovery and food industries possess several advantages, including unmatched chemical diversity with structural complexity and biological potency; occupy a complementary region of chemical space; the generation of libraries of natural product analogs, which might have enhanced drug-like properties; optimizing the regulation of natural product biosynthesis; lead to the discovery and better understanding of targets and pathways involved in the disease process, and can go straight from hit to drug [ 10 ]. Olivero-Acosta et al [ 6 ] were obtained 800 natural compound structures from the NatProd Collection database. They were performed a docking analysis using AtuoDock Vina software to identify interactions between these compounds and human epidermal growth factor receptors.…”

Effect of Different Extraction Methods and Geographical Origins on the Total Phenolic Yield, Composition, and Antimicrobial Activity of Sugarcane Bagasse Extracts

“…Baicalein, a compound found in all three samples, is significant because it has powerful antioxidant properties that can induce programmed cell death in breast and carcinogenic ovarian cells ( 32 ). Podototarin is a bisditerpenoid that can reduce rapid growth and proliferation ( 33 ). The VER sample had a higher content of Podototarin than that in the LA and TX samples.…”