Secoisolariciresinol diglucoside lignan concentrate of flaxseeds exhibits chemoprotective role in non-melanoma skin cancer through inhibition of CDK4 and upregulation of p53

Abstract

Cyclin-dependent kinases (CDKs) serve as target for various cancers including skin cancer. Secoisolariciresinoldiglucoside (SDG) and lignans exert anticancer effect on colon cancer through inhibition of CDKs. However, reports of SDG lignan concentrate (SLC) of Linum usitatissimum (L.) on skin cancer are not available. Hence, in this study, we evaluated the effect of SLC of L. usitatissimum on skin cancer, and determined the mechanism of action. Cell viability studies were done using the A-375 cell line. Skin cancer was induced by dimethyl Benz(a) anthracene and croton oil in female balb/c mice. SLC (5%) was administered from the 7^th to 16^th week after which we evaluated serum and tissue parameters. The IC50 value of SLC was found to be 93.7 μg/mL on the A-375 cell line. Skin cancer control animals exhibited increased tumor volume and burden and an increase in non-specific serum markers and tissue markers. Treatment with SLC decreased tumor volume and burden, and serum and tissue markers. Histopathological studies also depicted protection with SLC treatment. Docking studies revealed that SDG exhibits a good binding score with CDK4. Skin cancer control mice showed significantly increased CDK4 mRNA and decreased p53 mRNA levels which were prevented by SLC treatment. SLC exhibited a chemopreventive effect in skin cancer depicted by a reduction in serum biomarker, oxidative stress, collagen levels, tumor volume, tumor burden, and histopathological studies. These effects are mediated through the inhibition of CDK4 and upregulation of p53.