3-Methoxy Carbazole Impedes the Growth of Human Breast Cancer Cells by Suppressing NF-κB Signaling Pathway

Abstract

Breast cancer represents the most frequently occurring cancer globally among women. As per the recent report of the World Health Organization (WHO), it was documented that by the end of the year 2020, approximately 7.8 million females were positively diagnosed with breast cancer and in 2020 alone, 685,000 casualties were documented due to breast cancer. The use of standard chemotherapeutics includes the frontline treatment option for patients; however, the concomitant side effects represent a major obstacle for their usage. Carbazole alkaloids are one such group of naturally-occurring bioactive compounds belonging to the Rutaceae family. Among the various carbazole alkaloids, 3-Methoxy carbazole or C13H11NO (MHC) is obtained from Clausena heptaphylla as well as from Clausena indica. In this study, MHC was investigated for its anti-breast cancer activity based on molecular interactions with specific proteins related to breast cancer, where the MHC had predicted binding affinities for NF-κB with −8.3 kcal/mol. Furthermore, to evaluate the biological activity of MHC, we studied its in vitro cytotoxic effects on MCF-7 cells. This alkaloid showed significant inhibitory effects and induced apoptosis, as evidenced by enhanced caspase activities and the cellular generation of ROS. It was observed that a treatment with MHC inhibited the gene expression of NF-kB in MCF-7 breast cancer cells. These results suggest that MHC could be a promising medical plant for breast cancer treatment. Further studies are needed to understand the molecular mechanisms behind the anticancer action of MHC.

Ganetespib with Methotrexate Acts Synergistically to Impede NF-κB/p65 Signaling in Human Lung Cancer A549 Cells

“…The three-dimensional structures of the selected ligands, i.e., GAN [PubChem ID: 135564985] and MTX [PubChem ID: 126941], were retrieved from the PubChem database ( , accessed on 9 September 2022) in SDF file formats. The SDF files of the desired ligands were converted into PDB formats for using AutoDock Vina 4.0 [ 43 ]. We utilized the Linux subsystem command line and used MMFF94 force field for energy minimization (EM); after EM, we prepared the ligand molecules by using mgltools 1.5.6.…”

“…The population of potential ligand conformations/orientations at the binding site was estimated via docking. The binding pocket coordinates were chosen based on previously published literature, and the grid box was placed within a cubic box of magnitudes 40 × 40 × 40 [ 43 ]. The best-docked position with the lowest docked energy was chosen from nine conformations depending on the interacting residues, such as hydrogen bonds with a high binding affinity (kcal/mol).…”

Artificial Intelligence for Cancer Detection—A Bibliometric Analysis and Avenues for Future Research

“…With 1498 appearances, breast cancer is the ninth of the most often-used keywords. This is not surprising, since breast cancer is the most common carcinoma among women globally and comes with a low survival rate [62]. Breast cancer is followed by lung cancer (598 appearances), which causes the most cancer-related deaths worldwide [63].…”