Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Cancer-Preventive Activity of Argemone mexicana Linn Leaves and Interpretation of Its Orchestral Effect on TNF-α and NF-kB Signaling Modulation in DMBA/TPA Induced Skin Cancer Mice Model

Version 1 : Received: 17 November 2023 / Approved: 21 November 2023 / Online: 21 November 2023 (13:48:52 CET)

A peer-reviewed article of this Preprint also exists.

Kulshrestha, S.; Goel, A.; Siddiqi, N.J.; Fatima, S.; Sharma, B. Cancer-Preventive Activity of Argemone mexicana Linn Leaves and Its Effect on TNF-α and NF-κB Signalling. Cancers 2023, 15, 5654. Kulshrestha, S.; Goel, A.; Siddiqi, N.J.; Fatima, S.; Sharma, B. Cancer-Preventive Activity of Argemone mexicana Linn Leaves and Its Effect on TNF-α and NF-κB Signalling. Cancers 2023, 15, 5654.

Abstract

Introduction: Skin cancer is the 5th most common cancers in western countries with surge in the cases of occurrence with the passing time making it a global burden on health care system. In this present study, the cancer preventive activities of Argemone mexicana Linn (AM), which has been widely used by folklores to treat different ailments. Aim: The experiment advocates the cancer preventive activity of ethanolic extract of AM and to against DMBA/TPA induced skin cancer in mice model. Materials and Methods: Experimental animals were divided into doses group,100mg/kg B.W, 250mg/kg B.W, 500mg/kg B.W and 1000mg/kg B.W and subjected to toxic dose determination. The DMBA/TPA method was followed to induce the skin cancer in mice along with the feeding of non-toxic doses of 100mg/ kg, 250mg/kg, 500mg/kg mice were given as a pretreatment and 500mg/kg as a separate post treatment group as per body weight. The anti-cancerous activity was determined by different parameters on 0day, 30th day and 60th day including change in incidence of tumour induction, haematological parameters, histopathology and changes in pattern of TNF-α secretion and NF-kB (p65 subunit) signaling pathway in the blood serum. Results: The 1000 mg/kg BW was found to exhibit sub-acute toxicity. It was observed that the 500mg/kg BW pretreated group resisted and delayed the tumour formation for up to 8 weeks as compared to the Negative Control group where growth was seen in 4 weeks. The tumour burden was also found to be varying in a dose-dependent where on 60th day, Negative Control group and 100mg/kg BW was found to possess significantly high (p<0.001) tumour burden in comparison to the 500mg/kg BW group where tumour burden was not found till 60th day. The study was validated by body weight, blood parameters, histopathology and altered pattern in regulation of TNF-α and NF-kB signaling pathway which play an important role in cancer progression. The expression of TNF-α and p65 subunit of NF-kB signaling pathway was found to be reduced significantly in a dose dependent manner and found to be highly reduced in 500mg/kg BW group (p<0.001) as compared to Negative control. Conclusion: The 500mg/kg BW pretreated group was found to have significant results in comparison to 500mg/kg BW post treatment group. The study revealed effective cancer preventive activity of Argemone mexicana Linn leaves (AML) in the mice model and paved a pathway for molecular approaches which could be explored more in future studies.

Keywords

Argemone mexicana; cancer preventive; DMBA/TPA; mice model; Skin cancer

Subject

Medicine and Pharmacology, Complementary and Alternative Medicine

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