Pinus roxburghii and Nauplius graveolens Extracts Elevate Apoptotic Gene Markers in C26 Colon Carcinoma Cells Induced in a BALB/c Mouse Model

Abstract

The present study aimed to evaluate the chemopreventive potential of Pinus roxburghii branch (P. roxburghii) and Nauplius graveolens (N. graveolens) extracts against human colorectal cancer (CRC) induced by C26 murine cells in a BALB/c mouse model. Real-time qRT-PCR was used to evaluate the apoptotic pathway by measuring the relative mRNA expression levels of the Bcl-2, Bax, Cas3, NF-κB, and PI3k genes. At the termination of the 30-day period, blood samples were collected to assay the biomarkers. The results showed a significant increase (p < 0.05) in the levels of TGF-β, CEA, CA19-9, malondialdehyde, ALT, AST, ALP, urea, and creatinine in the positive control compared to the negative control group. In addition, the glutathione reductase activity and total antioxidant activity were reduced in the positive control compared to the negative control. The biomarkers mentioned above were restored to almost normal levels after administering a safe dose (1/10) of a lethal dose of P. roxburghii and N. graveolens extracts. Administration of one-tenth of the LD50 of P. roxburghii and N. graveolens extracts caused a significant upregulation of the expression of Bax and Cas-3 and downregulation of the Bcl-2, NF-ĸB, and PI3k genes vs. the GAPDH gene as a housekeeping gene compared to the control group. Furthermore, the Bax/Bcl-2 ratio increased upon treatment. After administration of P. roxburghii and N. graveolens at a safe dose (1/10) of a lethal dose, the results showed improvement in both body weight gain and a significant decrease (p < 0.05) in tumor volume. Histopathological changes supported these improvements. Conclusively, the research outputs show that P. roxburghii and N. graveolens extracts can be utilized as potential chemopreventive agents for CRC treatment by stimulating cancer cell apoptosis and suppressing CRC survival and proliferation.