Sunanda Kulshrestha ¹ Anjana Goel ^1,2* Subhadip Banerjee ³ Rohit Sharma ⁴ Mohammad Rashid Khan ⁵ Kow-Tong Chen ^6,7*

• ¹ Department of Biotechnology, GLA University, Mathura, India
• ² GLA University, Mathura, Uttar Pradesh, India
• ³ School of Natural Product Studies, Jadavpur University, Kolkata, West Bengal, India
• ⁴ Department of Rasa Shastra and Bhaishjya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
• ⁵ Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
• ⁶ Department of Occupational Medicine, Tainan Municipal Hospital, Tainan, Taiwan
• ⁷ Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Tainan County, Taiwan

Background: Cancer has emerged as one of the leading causes of fatality all over the world. Due to their synergistic effects on disease prevention by altering molecular pathways and immunomodulation without side effects, phytoconstituents are being studied. Ayurveda adresses Argemone mexicana Swarkshiri Linn. The Indian Medicinal Plant dictionary says traditional healers use it for psoriasis and its anti-inflammatory and anti-cancerous properties. Aim: This experiment aims to explore the cancer preventive activity and modulation in TNF-α expression patterns and NF-kB signaling pathway by Argemone mexicana Linn leaves extract in skin cancer cell lines (A431) and colon cancer cell lines (COLO 320DM)). Material and Methods: LC/MS study of Argemone mexicana Linn extracts was done to revealthe present anti-cancerous phytoconstituents. Network pharmacology analysis used Binding DB, STRING, DAVID, and KEGG for data mining to evaluate predicted compounds using functional annotation analysis followed by use of Cytoscape 3.2.1 to create “neighbourhood approach” and networks. The MNTD of these extracts was tested on L929 fibroblasts. Skin cancer (A431) and colon cancer (COLO 320DM) cell lines were examined to study the anti-cancerous property and to evaluate the TNF-α and NF-kB expression Results: Alkaloids like Berberine, Atropine, Argemexicin, and Argemonin were predicted in LC/MS analysis. In Network pharmacology analysis, enrichment was linked to the PI3-AKT pathway for both cancer types. MNTD was calculated at 1000μg/ml in L929. The ethanolic extract at 1000μg/ml was found to significantly inhibited skin cancer cell proliferation by 67% and colon cancer cells by 75% while reducing the TNF-α expression in both cell lines (p<0.001) and the NF-kB pathway (p<0.001) in case of TNF-α stimulated and non-stimulated cell lines. Conclusion: The abatement TNF-α expression and NF-kB transcription factor activation may contribute to reduced cancer cell proliferation. The study highlighted the anticancer activity of Argemone mexicana Linn in the cancer cell lines and paved a pathway for molecular approaches that could be explored more in In vivo studies.