Combinatorial antitumor effect of naringenin and curcumin elicit angioinhibitory activities in vivo.
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.
Functional Genomics and Cancer Biology Laboratory, Center for Medical Engineering, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
Kushi
K
Anand
Aditi
A
Sarkar
Anup
A
Kumar
Rashmi K
RK
Ambasta
Pravir
P
Kumar
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001201:Ascites / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D044950:Flavanones / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D051379:Mice; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D010537:Peritoneum / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D016019:Survival Analysis; D046509:Tissue Culture Techniques; D047368:Tumor Burden / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D044950:Flavanones; C005273:naringenin; D003474:Curcumin