Fatty Acid-enriched Euphorbia neriifolia Alleviates the NPIP-induced Lung Cancer Via Modulating Oxidative Stress and Apoptosis in Swiss Albino Mice
摘要
The current study aims to determine: (i) the effect of isolated compounds (ICs) from E. neriifolia leaf via TLC and HPTLC on the lung cancer target protein through molecular docking; (ii) the cytotoxicity (MTT; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and proapoptotic effect (DAPI; 4’-6-diamidino-2-phenylindole) of isolated linoleic acid (LA) in A549 cells; (iii) the in vivo anticancer potential of ENLE extract and LA against N-nitrosopiperidine (NPIP)-induced lung cancer in Swiss albino mice. Results revealed that LA was determined to be the better one among the studied ICs. This is due to its binding energy (-4.8 kcal/m and − 4.3 kcal/m), pharmacokinetic properties, and drug-likeliness. The LA decreased cell proliferation and viability above 400 µM after 24 and 48 h treatment. Apoptotic changes were revealed in treated adenocarcinoma (A549) cells with an IC50 dose of LA. The in-vivo analysis in Swiss albino mice (5–6 week old; 28–30 g) revealed that the administration of NPIP resulted in a reduction in body weight with a rise in serum levels of tumor markers (LDH, ADA, and 5’-ND), TP, and LPO. Metastasis markers (hexose, hexosamine, sialic acid, and uronic acid) with a concomitant reduction in the levels of enzymatic (SOD, CAT, and GPx), and non-enzymatic antioxidants (Vitamin E and Vitamin C) were also observed in response to NPIP administration. Moreover, high doses of ENLE, gefitinib (positive standard drug), and LA treatment significantly restored biochemical levels. Histological analyses showed restoration of normal architecture in the ENLE- and LA-treated groups. Immunohistology analyses revealed decreased p53 overexpression and normal CK7 levels compared with the NPIP group, indicating their protective effect. A high dose of ENLE after oral administration shows a remarkable decrease in tail length. The % tail DNA at a high dose of ENLE was determined to be 15.53 ± 0.11. Thus, the current study findings provide indications regarding the therapeutic potential of ENLE and LA against NPIP-induced lung cancer.