Combinatorial Antitumor Effect of Naringenin and Curcumin Elicit Angioinhibitory Activities In Vivo

• Published in: Nutrition and cancer Vol. 64; no. 5; pp. 714 - 724
• Main Authors: Anand, Kushi, Sarkar, Aditi, Kumar, Anup, Ambasta, Rashmi K, Kumar, Pravir
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis Group 01.07.2012; Taylor & Francis Ltd
• Subjects: albino; angiogenesis; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - adverse effects; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - therapeutic use; Animals; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - adverse effects; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; ascites; Ascites - etiology; Ascites - pathology; Ascites - prevention & control; body weight; Cancer; carcinoma; Carcinoma, Ehrlich Tumor - drug therapy; Carcinoma, Ehrlich Tumor - pathology; Carcinoma, Ehrlich Tumor - physiopathology; Cell Proliferation - drug effects; Cells; Chick Embryo; chorioallantoic membrane; Chorioallantoic Membrane - blood supply; Chorioallantoic Membrane - drug effects; curcumin; Curcumin - administration & dosage; Curcumin - adverse effects; Curcumin - pharmacology; Curcumin - therapeutic use; Female; Flavanones - administration & dosage; Flavanones - adverse effects; Flavanones - pharmacology; Flavanones - therapeutic use; heat shock proteins; immunomodulators; Liver - drug effects; Liver - pathology; Mice; naringenin; Neoplasm Transplantation; Neovascularization, Pathologic - etiology; Neovascularization, Pathologic - pathology; Neovascularization, Pathologic - prevention & control; oral administration; Peritoneum - blood supply; Peritoneum - drug effects; Peritoneum - pathology; Proteins; Rodents; Survival Analysis; therapeutics; Tissue Culture Techniques; Tumor Burden - drug effects; Tumors; vascular endothelial growth factors
• ISSN: 1532-7914; 0163-5581; 1532-7914
• DOI: 10.1080/01635581.2012.686648

Curcumin has long been used as an antioxidative, antiinflammatory, and modulator of pathological angiogenesis, whereas naringenin is a well-known immunomodulator. In this report, we investigated the effect of curcumin and naringenin on the growth of Ehrlich ascites carcinoma tumor model. To achieve this, Swiss albino mice were implanted intraperitoneally with 1 × 10⁶ Ehrlich ascites carcinoma cells followed by the administration of oral doses of naringenin and curcumin either individually (50 mg/kg body weight) or in combination (20 mg/kg body weight each). A marked reduction has been seen in the total number of cells (80%) and accumulation of ascetic fluid (55%) when these drugs were administered together. These drugs proved to be an effective angio-inhibitory compound and confirmed by different in vivo assay systems, viz. peritoneal/skin angiogenesis and chorioallantoic membrane assay. Antiangiogenic and antiproliferative effect of these compounds alone or in combination was further corroborated with immunoblot results where we confirmed the downregulation of vascular endothelial growth factor, Hif1α, heat shock protein 90, and p-Akt. Furthermore, treatment with naringenin and curcumin alone or in combination substantially improved hepatocellular architecture and no noticeable neoplastic lesions or cellular alteration were reported. These outcomes put forward a plausible clinical application of these diet-derived compounds, as both angioinhibitory and antitumor in association with conventional therapy.