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Artemisia carvifolia Buch silver nanoparticles downregulate the Rap2A gene in liver cancer
1Department of Bioinformatics and Biosciences, Faculty of Health and Life Sciences, Capital University of Science and Technology(CUST), Islamabad, 44000, Pakistan.
Abstract:
Liver cancer is the second main reason of death globally. In the current study, Rap2A protein a member of Ras Gtpase was selected as a drug target for liver cancer which has been identified as an oncogene in different types of tumors. The present study aimed to evaluate Artemisia carvifolia Buch extract and its silver nanoparticles against liver cancer targeting the Rap2A gene. The synthesized silver nanoparticles showed an absorbance peak at 450 nm by a UV-Vis spectrophotometer. SEM revealed that polyhedral silver nanoparticles had a size ranging from 80 ± 6 nm. Furthermore, amines, aldehydes, ketones and alcohols of Artemisia carvifolia were found involved in the reduction and stabilization of nanoparticles by FTIR. Moreover, XRD and EDX confirmed the cubic crystalline nature and particle elemental composition, respectively. Furthermore, the cytotoxicity against HePG2 cancer cell lines was also found significant with an IC50 value of 2.57 µM for silver nanoparticles and 11.57 µM for plant extract. The gene expression and protein level of Rap2A were also decreased in plant extract and nanoparticle-treated cells compared to control groups. The apoptotic potential of extract and nanoparticles was also determined by evaluating the apoptotic pathway genes and protein including BAX, caspase 3, 8 and 9. Significantly elevated levels of expression of these genes by real-time qPCR along with increased protein levels by ELISA were found. This is the first-ever report describing the synthesis and efficacy of silver nanoparticles of Artemisia carvifolia Buch against liver cancer.
Insights
Artemisia carvifolia silver nanoparticles effectively target Rap2A in liver cancer cells, reducing tumor growth and inducing apoptosis. This study presents a novel therapeutic approach for liver cancer treatment.
Area of Science:
- Oncology
- Nanotechnology
- Pharmacology
Background:
- Liver cancer is a leading global cause of cancer mortality.
- The Rap2A protein, a Ras GTPase, is implicated as an oncogene in various tumors, including liver cancer.
- Targeting Rap2A presents a potential therapeutic strategy for liver cancer.
Purpose of the Study:
- To synthesize and characterize silver nanoparticles (AgNPs) from Artemisia carvifolia Buch extract.
- To evaluate the anti-liver cancer efficacy of the A. carvifolia extract and its AgNPs, specifically targeting the Rap2A gene.
- To investigate the apoptotic potential of the A. carvifolia extract and AgNPs in liver cancer cells.
Main Methods:
- Synthesis and characterization of AgNPs using UV-Vis spectrophotometry, SEM, FTIR, XRD, and EDX.
- Cytotoxicity assessment against HePG2 liver cancer cell lines using IC50 values.
- Evaluation of Rap2A gene and protein expression levels.
- Analysis of apoptotic pathway genes (BAX, caspase 3, 8, 9) and proteins via real-time qPCR and ELISA.
Main Results:
- Characterized polyhedral AgNPs (80±6 nm) synthesized from A. carvifolia extract.
- Significant cytotoxicity observed: IC50 of 2.57 µM for AgNPs and 11.57 µM for the extract against HePG2 cells.
- Reduced Rap2A gene and protein expression in treated cells.
- Enhanced apoptosis indicated by elevated expression of BAX, caspase 3, 8, and 9 at both gene and protein levels.
Conclusions:
- A. carvifolia extract-mediated silver nanoparticles demonstrate significant anti-liver cancer activity.
- The synthesized AgNPs effectively target and downregulate Rap2A, a key oncogene in liver cancer.
- This study establishes a novel, effective, and natural therapeutic approach using A. carvifolia derived AgNPs for liver cancer treatment.
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