Antitumor Activity of Luteolin Against Ehrlich Solid Carcinoma in Rats via Blocking Wnt/β-Catenin/SMAD4 Pathway.

Abstract

Background Ehrlich solid carcinoma (ESC) is characterized by rapid proliferation and a short survival time. Because Ehrlich ascites carcinoma (EAC) resembles human cancer cells, Ehrlich solid and ascetic forms are commonly used to determine the anticancer effects of various compounds. Luteolin is a flavonoid compound found in many dietary sources, including carrots, peppers, celery, olive oil, peppermint, and oregano. Luteolin has potent anti-inflammatory, antidiabetic, antitumor, and antiapoptotic activities. Aims This study aims to investigate the antitumor activity of luteolin against ESC in rats by affecting the Wnt/β-catenin/SMAD4 pathway. Methods We introduced 0.15 ml of Ehrlich cells (2 × 106) ESC into the left hind thighs of rats. After eight days of inoculation, the rats orally received 25 mg/kg of luteolin daily. We stained sections of tumor tissues with Masson's trichrome. We used another part of the tumor tissue to assess gene and protein expression of Wnt, β-catenin, E-cadherin, and SMAD4. Results Treatment of carcinoma rats with luteolin increased the mean survival time and reduced tumor volume and weight. In addition, examination of tumor tissue stained with Masson's trichrome showed loosely to densely packed collagen fibers in between neoplastic cells and scattered papillary expansion of a loose blue band of collagen expression along the covering adipose connective tissue and extending in a fine strand in between muscle fibers, which was ameliorated by treating rats with luteolin. Finally, treating ESC in rats with luteolin overexpressed E-cadherin and downregulated Wnt, β-catenin, and SMAD4. Conclusions We found luteolin has antineoplastic activity against ESC by reducing tumor size and weight while improving the structure of muscle cells. It works by suppressing Wnt, β-catenin, and SMAD4, resulting in decreased tumor cell proliferation and differentiation. Additionally, luteolin overexpresses E-cadherin, leading to reduced tumor cell invasion and metastasis.