The Protective Potential of Terpenoid-Rich Canarium odontophyllum Miq. Leaves against 7,12-Dimethylbenz[a]anthracene and Ultraviolet B-induced Two-stage Skin Carcinogenesis in BALB/c Mice

Abstract

Non-melanoma skin cancer remains among the most prevalent malignancies globally. This study investigated the protective potential of a terpenoid-rich extract from Canarium odontophyllum Miq. leaves (TRCO) in a 7,12-dimethylbenz[a]anthracene (DMBA) and ultraviolet B (UVB)-induced two-stage skin carcinogenesis (DMBA/UVB) model using BALB/c mice, focusing primarily on its action during the tumor promotion stage. Mice were topically treated with TRCO at 100 µg (TRCO100) and 200 µg (TRCO200) prior to DMBA/UVB exposure. The protective activities were evaluated based on macroscopic skin changes, histopathology, antioxidant enzyme activities, melanogenesis parameters, and expression levels of key tumor-associated markers (p53, Ki67, and VEGF). TRCO treatment significantly reduced DMBA/UVB-induced erythema, epidermal hyperplasia, and melanogenesis. TRCO modulated antioxidant enzyme activities (total SOD, CAT, GSH-Px and GST) and significantly lowered oxidative stress biomarkers. Expression of p53, Ki67, and VEGF was markedly modulated, with the TRCO100 group showing pronounced variations. These findings suggest that TRCO exerts promising protective potential against preneoplastic skin progression in a two-stage carcinogenesis model, most likely through integrated antioxidant, anti-inflammatory, and antiproliferative tissue mechanisms.