Abstract
Background: Angiogenesis plays an important role in the pathogenesis of breast cancer. For growth, tumor requires the formation of new blood vessels, which are stimulated by angiogenic factors to initiate the proliferation of endothelial cells. The major contributors to angiogenesis are the vascular endothelial growth factor (VEGF) and its receptors, which promote cell proliferation, migration, permeability and survival. Controlling tumor-associated angiogenesis and metastasis are promising tactics in limiting cancer progression. Curcumin, a polyphenolic compound derived from the spice plant Curcuma longa, displays multiple actions on solid tumours including anti-angiogenic effects. In this study we evaluated the benefits of curcumin treatment on tumor growth and angiogenesis in breast cancer. Methods: MDA-MB-231 breast cancer cell line was cultured and cell viability was measured by MTT assay after incubation with different concentrations of curcumin (25 uM, 50 uM, 100 uM). We performed an in vivo study implanting cells in athymic nude mice. Mice were treated with 300 mg/kg of curcumin (n = 5) or vehicle (n = 8) daily, starting in the same day as tumor implantation and continued for 21 days. Tumors were measured with a digital caliper on day 7, 14 and 21 and the animals underwent SPECT scanning with Tc-99m tagged VEGF-c to detect in vivo angiogenesis (expression of VEGFR2/3). In addition, the markers of angiogenesis (VEGF-A, VEGF-C, VEGFR2, VEGFR3 and von Willebrand Factor (vWF)) and cell proliferation (Ki-67) were evaluated by immunohistochemistry in mammary tumor tissues. Results: Curcumin treatment in vitro was able to significantly decrease cell viability, after 4 hours of exposure, maintaining its efficacy at higher doses after 24 hours exposure (p<0.05). After 21 days of treatment, curcumin retards the breast tumor growth, showed by the slower tumoral development of the treated group compared to the control group (p<0.05). The mean tumor volume of control and treated animals were 282.00 ± 88.53 mm3 232.5± 53.2 mm3, respectively. Animals treated with curcumin showed lower activity of Tc-99-VEGF-C in the tumors compared to that of the animals that were treated with vehicle. The intensity of radioactivity in the control animals was 183.55 ± 20.92%, while the intensity of radioactivity in animals treated with curcumin was 134.9 ± 10.3%. Although there was difference in the radioactivity in the tumors between the two group, statistically significant difference was not achieved (p>0.05). However, decrease of VEGF-A, VEGF-C and VEGFR2 in curcumin treated mice was confirmed by immunohistochemistry (p<0.05). In addition, there was a decrease of micro-vessel density (vWF) and cell proliferation (Ki-67) in curcumin treated tumors (p<0.05). Conclusion: In summary, our results demonstrate that curcumin affect the viability of the breast cancer cells in vitro. In addition, in vivo study, curcumin is able to retards the breast tumor growth when compared to the control group. Both SPECT and histochemical analysis indicate decrease in angiogenesis following treatment with curcumin.
Citation Format: Lívia Carvalho Ferreira, Ali Syed Arbab, Bruna Victorasso Jardim-Perassi, Thaiz Ferraz Borin, Naiane Nascimento Gonçalves, Ravi Sankara Varma Nadimpalli, Debora Aparecida Pires de Campos Zuccari. Effect of curcumin on the tumor growth and angiogenesis of breast cancer. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A02. doi:10.1158/1538-7445.CHTME14-A02
