Immunomodulatory and Anti-cancer Potency of Lysergol on Benzo[ <i>a</i> ]pyrene-induced Lung Carcinogenesis and Attenuation of Tumor Progression in Mice Model

Background Benzo[ a ]pyrene (B[a]P), a polycyclic aromatic hydrocarbon exposure, is a major public health issue globally, particularly as a result of its connection to lung cancer. Individuals exposed to higher levels of B[a]P exhibit markedly elevated risks of developing pulmonary carcinoma. Globally, pulmonary carcinoma continues to be one of the top causes of cancer-related fatalities, and mitigating B[a]P exposure is decisive for alleviating this ailment. Objectives The therapeutic potency of lysergol, a clavine alkaloid phytochemical, against B[a]P-triggered lung carcinoma was analyzed. Materials and Methods Healthy Swiss albino mice were subjected to B[a]P exposure and subsequently treated with lysergol to evaluate its effectiveness in mitigating lung cancer. We recorded body mass, lung mass, and tumor occurrence, while also quantifying immunoglobulin and tumor marker levels to assess the anti-cancer properties of lysergol. To understand its impact on B[a]P metabolism and detoxification, we measured Phase I and II enzymes. Additionally, we quantified the prognostic tumor biomarkers carcinoembryonic antigen (CEA) and cytokeratin fragment 21-1 (CYFRA 21-1) in B[a]P-treated mice, as well as inflammatory cytokines to assess the anti-inflammatory efficacy of lysergol. Mitochondrial enzyme activity and proliferating cell nuclear antigen (PCNA), nuclear factor kappa B (NF-κB), cytochrome P450 1A1 (CYP1A1), and nuclear factor erythroid 2-related factor 2 (NRF2) levels were assayed to evaluate the progression of the tumor. Results Lung tissue histology analysis was performed to confirm the anti-cancer effects of lysergol. Our findings revealed that both pretreatment and post-treatment with lysergol prevented tumor occurrence and regulated immunoglobulin and tumor biomarker levels in B[a]P-exposed mice. Phase I enzymes decreased significantly, while Phase II enzymes increased following lysergol treatment. Additionally, lysergol treatment led to the suppression of prognostic biomarkers CEA and CYFRA 21-1, as well as inflammatory cytokines in the B[a]P-exposed animals. The treatment also resulted in decreased mitochondrial enzyme levels, thereby helping to maintain redox balance. Furthermore, lysergol reduced PCNA, NF-κB, CYP1A1, and NRF2 levels, indicating its inhibitory effect on B[a]P-induced tumor progression. Histopathological results supported our other analyses, confirming that lysergol treatment effectively reduced carcinoma initiation and progression in B[a]P-triggered mice. Conclusion In conclusion, lysergol demonstrates considerable potential as an anti-cancer agent, effectively mitigating B[a]P-triggered lung carcinoma in a mouse model, and warrants further investigation for its usage as a therapeutic drug for lung cancer.