Capsicum annuum Regulates Tumor Growth Through Modulation of TLR4/PI3K Signaling in a Lewis Lung Carcinoma Mouse Model

Since lung cancer remains a leading cause of cancer-related mortality, effective adjunct strategies against this disease are needed. This study evaluated an extract prepared from organically cultivated Capsicum annuum treated with deep-seawater-derived ion minerals during cultivation (ODSW-CE) in Lewis lung carcinoma (LLC1) cells and LLC1 tumor-bearing mice. Targeted HPLC-DAD analysis identified and quantified lutein and β-carotene as representative carotenoids. ODSW-CE reduced MTT-derived cell viability and colony-forming ability in vitro and suppressed tumor growth in vivo. In tumor-bearing mice, ODSW-CE was associated with lower hematological inflammatory indices, reduced TNF-α and IL-1β levels in plasma and lung tissue, and attenuated histopathological alterations in tumor and lung tissues. These changes were accompanied by reduced expression of proteins associated with TLR4/MyD88/NF-κB signaling. ODSW-CE also modulated survival and apoptosis-related proteins, decreasing PI3K, p-Akt, and p-mTOR expression, increasing Bax and cleaved caspase-3 expression, and decreasing Bcl-2 expression. Additionally, in tumor tissue, Keap1 expression increased, whereas Nrf2, xCT, and GPX4 expression decreased. Overall, ODSW-CE suppressed LLC1 tumor growth and was associated with coordinated modulation of tumor-associated inflammatory signaling, survival pathways, apoptosis-related proteins, and redox defense.