A gallotannin-rich fraction from Caesalpinia spinosa (Molina) Kuntze displays cytotoxic activity and raises sensitivity to doxorubicin in a leukemia cell line

BMC Complementary and Alternative Medicine

Susana Fiorentino²  John Fredy Hernandez²  Claudia Patricia Urueña²  Luis Miguel Pombo¹  Diana M Castañeda² 

[1]Grupo de Farmacología Vegetal, Fundación Universitaria Juan N. Corpas, Bogotá, Colombia, Carrera 111 # 159A61

[2]Grupo de Inmunobiología y Biología Celular, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, Colombia, Carrera 7 N. 43-82 Building 52, Office 608

关键词: Leukemia;    Tumor;    C.spinosa;    Gallotannins;    Adjuvants;   

Others  :  1232717
DOI  :  10.1186/1472-6882-12-38

 received in 2011-09-27, accepted in 2012-04-10,  发布年份 2012

【 摘 要 】

Background

Enhancement of tumor cell sensitivity may help facilitate a reduction in drug dosage using conventional chemotherapies. Consequently, it is worthwhile to search for adjuvants with the potential of increasing chemotherapeutic drug effectiveness and improving patient quality of life. Natural products are a very good source of such adjuvants.

Methods

The biological activity of a fraction enriched in hydrolysable polyphenols (P2Et) obtained from Caesalpinia spinosa was evaluated using the hematopoietic cell line K562. This fraction was tested alone or in combination with the conventional chemotherapeutic drugs doxorubicin, vincristine, etoposide, camptothecin and taxol. The parameters evaluated were mitochondrial depolarization, caspase 3 activation, chromatin condensation and clonogenic activity.

Results

We found that the P2Et fraction induced mitochondrial depolarization, activated caspase 3, induced chromatin condensation and decreased the clonogenic capacity of the K562 cell line. When the P2Et fraction was used in combination with chemotherapeutic drugs at sub-lethal concentrations, a fourfold reduction in doxorubicin inhibitory concentration 50 (IC₅₀) was seen in the K562 cell line. This finding suggested that P2Et fraction activity is specific for the molecular target of doxorubicin.

Conclusions

Our results suggest that a natural fraction extracted from Caesalpinia spinosa in combination with conventional chemotherapy in combination with natural products on leukemia cells may increase therapeutic effectiveness in relation to leukemia.

【 授权许可】

   
2012 Castañeda et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】

• [1]Chanwitheesuk A, Teerawutgulrag A, Kilburn J, Rakariyatham N: Antimicrobial gallic acid from Caesalpinia mimosoides lamk. Food Chem 2007, 100:1044-1048.
• [2]Kloucek P, Polesny Z, Svobodova B, Vlkova E, Kokoska L: Antibacterial screening of some Peruvian medicinal plants used in Calleria District. J Ethnopharmacol 2005, 99(2):309-312.
• [3]Zhang J, Li L, Kim SH, Hagerman AE, Lu J: Anti-cancer, anti-diabetic and other pharmacologic and biological activities of penta-galloyl-glucose. Pharm Res 2009, 26(9):2066-2080.
• [4]Clifford MN, Stoupi S, Kuhnert N: Profiling and characterization by LC-MSn of the galloylquinic acids of green tea, tara tannin, and tannic acid. J Agric Food Chem 2007, 55(8):2797-2807.
• [5]Gali-Muhtasib HU, Yamout SZ, Sidani MM: Tannins protect against skin tumor promotion induced by ultraviolet-B radiation in hairless mice. Nutr Canc 2000, 37(1):73-77.
• [6]Locatelli C, Rosso R, Santos-Silva MC, de Souza CA, Licinio MA, Leal P, Bazzo ML, Yunes RA, Creczynski-Pasa TB: Ester derivatives of gallic acid with potential toxicity toward L1210 leukemia cells. Bioorg Med Chem 2008, 16(7):3791-3799.
• [7]Inoue M, Suzuki R, Koide T, Sakaguchi N, Ogihara Y, Yabu Y: Antioxidant, gallic acid, induces apoptosis in HL-60RG cells. Biochem Biophys Res Commun 1994, 204(2):898-904.
• [8]Pellegrina CD, Padovani G, Mainente F, Zoccatelli G, Bissoli G, Mosconi S, Veneri G, Peruffo A, Andrighetto G, Rizzi C, et al.: Anti-tumour potential of a gallic acid-containing phenolic fraction from Oenothera biennis. Cancer Lett 2005, 226(1):17-25.
• [9]Chia YC, Rajbanshi R, Calhoun C, Chiu RH: Anti-neoplastic effects of gallic acid, a major component of Toona sinensis leaf extract, on oral squamous carcinoma cells. Molecules 2010, 15(11):8377-8389.
• [10]Shanafelt TD, Lee YK, Call TG, Nowakowski GS, Dingli D, Zent CS, Kay NE: Clinical effects of oral green tea extracts in four patients with low grade B-cell malignancies. Leuk Res 2006, 30(6):707-712.
• [11]Kashiwada Y, Nonaka G, Nishioka I, Chang JJ, Lee KH: Antitumor agents, 129. Tannins and related compounds as selective cytotoxic agents. J Nat Prod 1992, 55(8):1033-1043.
• [12]Kelkel M, Jacob C, Dicato M, Diederich M: Potential of the dietary antioxidants resveratrol and curcumin in prevention and treatment of hematologic malignancies. Molecules 2010, 15(10):7035-7074.
• [13]Chaudhari M, Mengi S: Evaluation of phytoconstituents of Terminalia arjuna for wound healing activity in rats. Phytother Res 2006, 20(9):799-805.
• [14]Uruena C, Cifuentes C, Castaneda D, Arango A, Kaur P, Asea A, Fiorentino S: Petiveria alliacea extracts uses multiple mechanisms to inhibit growth of human and mouse tumoral cells. BMC Compl Alternative Med 2008, 8:60. BioMed Central Full Text
• [15]Sharma OP, Bhat TK, Singh B: Thin-layer chromatography of gallic acid, methyl gallate, pyrogallol, phloroglucinol, catechol, resorcinol, hydroquinone, catechin, epicatechin, cinnamic acid, p-coumaric acid, ferulic acid and tannic acid. J Chrom A 1998, 822:167-171.
• [16]Yang LL, Lee CY, Yen KY: Induction of apoptosis by hydrolyzable tannins from Eugenia jambos L. on human leukemia cells. Cancer Lett 2000, 157(1):65-75.
• [17]Kim NS, Jeong SI, Hwang BS, Lee YE, Kang SH, Lee HC, Oh CH: Gallic acid inhibits cell viability and induces apoptosis in human monocytic cell line U937. J Med Food 2011, 14(3):240-246.
• [18]Serrano A, Palacios C, Roy G, Cespon C, Villar ML, Nocito M, Gonzalez-Porque P: Derivatives of gallic acid induce apoptosis in tumoral cell lines and inhibit lymphocyte proliferation. Arch Biochem Biophys 1998, 350(1):49-54.
• [19]Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, Blagosklonny MV, El-Deiry WS, Golstein P, Green DR, et al.: Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ 2009, 16(1):3-11.
• [20]Chen R, Gandhi V, Plunkett W: A sequential blockade strategy for the design of combination therapies to overcome oncogene addiction in chronic myelogenous leukemia. Cancer Res 2006, 66(22):10959-10966.
• [21]Pan MH, Lin JH, Lin-Shiau SY, Lin JK: Induction of apoptosis by penta-O-galloyl-beta-D-glucose through activation of caspase-3 in human leukemia HL-60 cells. Eur J Pharmacol 1999, 381(2-3):171-183.
• [22]Luo T, Wang J, Yin Y, Hua H, Jing J, Sun X, Li M, Zhang Y, Jiang Y: (-)-Epigallocatechin gallate sensitizes breast cancer cells to paclitaxel in a murine model of breast carcinoma. Breast Cancer Res 2010, 12(1):R8. BioMed Central Full Text
• [23]Liang G, Tang A, Lin X, Li L, Zhang S, Huang Z, Tang H, Li QQ: Green tea catechins augment the antitumor activity of doxorubicin in an in vivo mouse model for chemoresistant liver cancer. Int J Oncol 2010, 37(1):111-123.