Investigating the Anticancer Activity of G-Rh1 Using In Silico and In Vitro Studies (A549 Lung Cancer Cells)

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 23; p. 8311
• Main Authors: Nahar, Jinnatun, Boopathi, Vinothini, Murugesan, Mohanapriya, Rupa, Esrat Jahan, Yang, Deok Chun, Kang, Se Chan, Mathiyalagan, Ramya
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28-11-2022; MDPI
• Subjects: A549 Cells; Adenocarcinoma; ADMET; Alzheimer's disease; Analysis; Angiogenesis; Animals; anti-lung cancer; Antitumor activity; Apoptosis; autodock vina; BAX protein; Biocompatibility; Biological activity; Breast cancer; Cancer; Cancer cells; Cancer therapies; Caspase-3; Caspase-9; Cell death; Cell differentiation; Cell division; Colorectal cancer; Cytotoxicity; Gelatinase B; Gene expression; Ginseng; Ginsenosides - chemistry; Humans; Hydrogen bonds; In vitro methods and tests; Insilco; Ischemia; Kinases; Liver cancer; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Macrophages; Malignancy; Metastases; Metastasis; Mice; Molecular dynamics; Molecular weight; Motility; Muscle contraction; Muscles; Muscular function; Natural products; Oncology, Experimental; p53 Protein; Panax - metabolism; Panax ginseng; Pharmacokinetics; Prevention; Principal components analysis; Protein kinases; Protein-serine/threonine kinase; Proteins; rho-Associated Kinases - metabolism; rhoA GTP-Binding Protein - metabolism; RhoA protein; ROCK1; Signal transduction; Tumor proteins; South Korea; Japan; anti-lung cancer; autodock vina; ROCK1; Insilco; ADMET
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27238311

Ginsenoside Rh1 (G-Rh1), a possible bioactive substance isolated from the Korean
Meyer, has a wide range of pharmacological effects. In this study, we have investigated the anticancer efficacy of G-Rh1 via in silico and in vitro methodologies. This study mainly focuses on the two metastatic regulators, Rho-associated protein kinase 1 (ROCK1) and RhoA, along with other standard apoptosis regulators. The ROCK1 protein is a member of the active serine/threonine kinase family that is crucial for many biological processes, including cell division, differentiation, and death, as well as many cellular processes and muscle contraction. The abnormal activation of ROCK1 kinase causes several disorders, whereas numerous studies have also shown that RhoA is expressed highly in various cancers, including colon, lung, ovarian, gastric, and liver malignancies. Hence, inhibiting both ROCK1 and RhoA will be promising in preventing metastasis. Therefore, the molecular level interaction of G-Rh1 with the ROCK1 and RhoA active site residues from the preliminary screening clearly shows its inhibitory potential. Molecular dynamics simulation and principal component analysis give essential insights for comprehending the conformational changes that result from G-Rh1 binding to ROCK1 and RhoA. Further, MTT assay was employed to examine the potential cytotoxicity in vitro against human lung cancer cells (A549) and Raw 264.7 Murine macrophage cells. Thus, G-Rh1 showed significant cytotoxicity against human lung adenocarcinoma (A549) at 100 µg/mL. In addition, we observed an elevated level of reactive oxygen species (ROS) generation, perhaps promoting cancer cell toxicity. Additionally, G-Rh1 suppressed the mRNA expression of RhoA, ROCK1, MMP1, and MMP9 in cancer cell. Accordingly, G-Rh1 upregulated the p53, Bax, Caspase 3, caspase 9 while Bcl2 is downregulated intrinsic pathway. The findings from our study propose that the anticancer activity of G-Rh1 may be related to the induction of apoptosis by the RhoA/ROCK1 signaling pathway. As a result, this study evaluated the functional drug-like compound G-Rh1 from
in preventing and treating lung cancer adenocarcinoma via regulating metastasis and apoptosis.