Induction of apoptosis in AGS and HepG2 cancer cells using Indole-3-Carbinol and Angelica keiskei extracts

Abstract

One of the most common diseases in the world is cancer. Action is still required in the face of the formidable global health challenge posed by cancer. Cancer is a disease that occurs when specific body cells proliferate abnormally out of control and migrate to other body areas. Following the standard view of the disease, cancer is an assortment of progressive genetic abnormalities caused by mutations in tumor-suppressor genes, oncogenes, and chromosomal abnormalities. Cancer chemoprevention uses natural or biological compounds to reduce the risk of developing cancer in healthy people. Chemopreventive drugs prevent cancer growth by preventing DNA damage, which results in spite, or by reversing or preventing the division of premalignant cells with DNA damage. Most of the pharmaceuticals employed nowadays are derived from plants, making them one of the more significant sources of medicine. Differential drug response and safe dosages are the main challenges to such prediction. It is safe to treat with IC50 doses to avoid the side effects of the drugs that kill normal cells and cancer cells. Clinical studies have shown that phytochemicals and herbs are the most efficient way to treat cancer, whether added to chemotherapy or taken separately to boost the immune system without any side effects. Gastric cancer is the second-leading cause of cancer-related deaths globally. One known fact is that Helicobacter pylori infects the stomach's inner lining and causes cancer. In this research, Indole-3-Carbinol is used as an anticancer drug against the AGS cancer cells. Cell viability was performed to check the compound's anticancer activity. DNA fragmentation was utilized to assess DNA degradation, and DAPI labeling was employed to identify nuclear condensation. The qPCR technique was used to measure apoptotic gene expression. I3C demonstrated a strong affinity for the apoptotic protein 3DCY per molecular docking study. This work explores the remarkable anticancer, antioxidant, and antibacterial properties and the safest drug delivery applications. Angelica keiskei Crude was extracted using the subcritical water extraction method. Antioxidant activity was evaluated using a DPPH radical scavenging assay. MTT assay was done to check the compound's anticancer activity on MDA-MB-231 cells. HAp was used for drug delivery. UV-Vis study was performed to check the photothermal efficacy, drug loading, and releasing capacity. A hemolysis research was conducted to determine the biocompatibility and safety of the compounds. Molecular docking was performed to check the binding affinity with the bacterial proteins. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. In the present study, the Angelica keiskei extract’s active compound identified by GC-MS is 3, - Dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP) induced apoptosis in HepG2 cells. Cell viability was decreased in a dose-dependent manner after the MTT test. The study's main emphasis, the Antibody Apoptotic Array that has checked the 43 genes' expression together, identified significant changes in apoptotic proteins. Western blot analysis and molecular docking further confirmed the expression of apoptotic proteins and binding affinity. This work is distinct and has never been done using the mentioned cells and techniques. This can help further study the precise molecular mechanism of action.