Combination Of Natural Compounds Research Articles

Abstract 802: Synergistic effect of curcumin on FL118 efficacy in colon cancer

Abstract Colorectal cancer is the third most commonly diagnosed cancer in the United States and may cause about 50,830 deaths in 2013. Therefore, there is an unmet need for new therapeutic strategies. Combination of natural compounds with pharmacological small molecular inhibitors to increase anticancer efficacy while minimizing toxicity is an attractive approach for management of cancer. Curcumin, a natural dietary compound, has been shown to inhibit multiple cancer cell signaling pathways involved in survival, proliferation, apoptosis, angiogenesis and metastasis. FL118, a novel camptothecin derivative and an IAP (inhibitor of apoptosis) inhibitor, significantly attenuates colon cancer cell growth in vitro and tumor growth in vivo. In the current study, we report that curcumin enhances FL118 anti-cancer efficiency in colon cancer cell models. MTT and cell death detection ELISA assays were used for quantification of cell viability and apoptosis, respectively, in colon cancer HCT8 and SW620 cells. The synergistic effect of curcumin in combination with FL118 treatment on colon cancer growth inhibition was further analyzed by the Combination Index (CI) equation developed by Chou-Talalay using a CalcuSyn program (Biosoft, Cambridge, UK). Our data demonstrated that curcumin shows a synergistic growth inhibitory effect with FL118 in multiple colon cancer cells (p<0.05). Furthermore, combinational treatment can significantly enhance apoptotic cell death induced in comparison with either FL118 or curcumin treatment alone (p<0.05). In HCT8 colon cancer cells, a combination of 10µM curcumin with 0.3-20 nM FL118 treatment for 72 h showed a strong synergistic effect (CI < 0.5) in cell growth inhibition. Mechanistically, the combination treatment-enhanced cell growth inhibition and apoptosis are associated with alteration of the expression of cell death and cell cycle related genes. In conclusion, we propose that combination of curcumin with FL118 might provide a novel therapeutic strategy in colon cancer treatment. Citation Format: Xiang Ling, Nishant Gandhi, Boyang Jiao, Dhyan Chandra, Fengzhi Li. Synergistic effect of curcumin on FL118 efficacy in colon cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 802. doi:10.1158/1538-7445.AM2014-802

Terpenes from Copaifera Demonstrated in Vitro Antiparasitic and Synergic Activity

To discover new possible therapies for Chagas' disease, we evaluated against all Trypanosoma cruzi life stages the in vitro trypanocidal and synergistic activity of terpenes isolated from Copaifera oleoresins collected in the Amazon and investigated their possible mechanism of action. Seven acid diterpenes and one sesquiterpene were tested. Terpenes promoted changes in oxidative metabolism followed by autophagic processes in the parasite cell leading to selective death. Furthermore, they were more effective against replicative forms, in particular amastigotes. A synergistic effect occurred. Cytotoxicity to erythrocytes and nucleated cells was moderate. This is the first study showing synergic activity between two terpenes against T. cruzi. Combinations of natural compounds can show high activity and may lead to new alternative treatments in the future.

Inhibition of glioma cell line A-172 MMP activity and cell invasion in vitro by a nutrient mixture

Standard multimodality therapy of gliomas is associated with poor patient survival and significant toxicity. Abnormal expression of matrix metalloproteinases is associated with tumor growth and invasion. Based on reported antitumor properties, we investigated the effect of a combination of natural compounds (NM), primarily composed of lysine, proline, ascorbic acid, and green tea extract in vitro on glioma cell line A-172, by measuring MMP secretion, invasion through Matrigel, and cell proliferation. Glioma cells A-172 (ATCC) were grown in modified Dulbecco's Eagle medium with 10% fetal bovine serum and antibiotics and treated with NM at 0, 10, 50, 100, 500, and 1000 microg/mL concentration in triplicate at each dose. Cell proliferation was assayed by MTT, MMP secretion by zymography, invasion through Matrigel, and morphology by H&E staining. Zymography showed one band corresponding to MMP-2, which was inhibited by NM in a dose-dependent fashion, with virtual total inhibition at 500-microg/mL concentration. Invasion through Matrigel was completely inhibited at 1000 microg/mL NM. NM was not toxic to glioma cell line A-172 at lower concentrations and exhibited toxicity of 50% over the control at 1000 microg/mL. NM significantly inhibited MMP secretion and invasion-important parameters for cancer prevention, suggesting a possible therapeutic role.