Skip to main content
Top
Published in: BMC Cancer 1/2006

Open Access 01-12-2006 | Research article

A new extract of the plant calendula officinalis produces a dual in vitroeffect: cytotoxic anti-tumor activity and lymphocyte activation

Authors: Eva Jiménez-Medina, Angel Garcia-Lora, Laura Paco, Ignacio Algarra, Antonia Collado, Federico Garrido

Published in: BMC Cancer | Issue 1/2006

Login to get access

Abstract

Background

Phytopharmacological studies of different Calendula extracts have shown anti-inflamatory, anti-viral and anti-genotoxic properties of therapeutic interest. In this study, we evaluated the in vitro cytotoxic anti-tumor and immunomodulatory activities and in vivo anti-tumor effect of Laser Activated Calendula Extract (LACE), a novel extract of the plant Calendula Officinalis (Asteraceae).

Methods

An aqueous extract of Calendula Officinalis was obtained by a novel extraction method in order to measure its anti-tumor and immunomodulatory activities in vitro. Tumor cell lines derived from leukemias, melanomas, fibrosarcomas and cancers of breast, prostate, cervix, lung, pancreas and colorectal were used and tumor cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of LACE on human peripheral blood lymphocyte (PBL) proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in LACE-treated cells. In vivo anti-tumor activity was evaluated in nude mice bearing subcutaneously human Ando-2 melanoma cells.

Results

The LACE extract showed a potent in vitro inhibition of tumor cell proliferation when tested on a wide variety of human and murine tumor cell lines. The inhibition ranged from 70 to 100%. Mechanisms of inhibition were identified as cell cycle arrest in G0/G1 phase and Caspase-3-induced apoptosis. Interestingly, the same extract showed an opposite effect when tested on PBLs and NKL cell line, in which in vitro induction of proliferation and activation of these cells was observed. The intraperitoneal injection or oral administration of LACE extract in nude mice inhibits in vivo tumor growth of Ando-2 melanoma cells and prolongs the survival day of the mice.

Conclusion

These results indicate that LACE aqueous extract has two complementary activities in vitro with potential anti-tumor therapeutic effect: cytotoxic tumor cell activity and lymphocyte activation. The LACE extract presented in vivo anti-tumoral activity in nude mice against tumor growth of Ando-2 melanoma cells.
Appendix
Available only for authorised users
Literature
1.
go back to reference Park EJ, Pezzuto JM: Botanicals in cancer chemoprevention. Cancer Metastasis Rev. 2002, 21: 231-255. 10.1023/A:1021254725842.CrossRefPubMed Park EJ, Pezzuto JM: Botanicals in cancer chemoprevention. Cancer Metastasis Rev. 2002, 21: 231-255. 10.1023/A:1021254725842.CrossRefPubMed
2.
go back to reference Huang KC: The Pharmacology of Chinese Herbs. 1999, CRC Press, Boca Raton, 457-483. 2 Huang KC: The Pharmacology of Chinese Herbs. 1999, CRC Press, Boca Raton, 457-483. 2
3.
go back to reference Demeule M, Michaud-Levesque J, Annabi B, Gingras D, Boivin D, Jodoin J, Lamy S, Bertrand Y, Beliveau R: Green tea catechins as novel antitumor and antiangiogenic compounds. Curr Med Chem Anti-Cancer Agents. 2002, 2: 441-463. 10.2174/1568011023353930.CrossRefPubMed Demeule M, Michaud-Levesque J, Annabi B, Gingras D, Boivin D, Jodoin J, Lamy S, Bertrand Y, Beliveau R: Green tea catechins as novel antitumor and antiangiogenic compounds. Curr Med Chem Anti-Cancer Agents. 2002, 2: 441-463. 10.2174/1568011023353930.CrossRefPubMed
4.
go back to reference Dorai T, Aggarwal BB: Role of chemopreventive agents in cancer therapy. Cancer Lett. 2004, 215: 129-140. 10.1016/j.canlet.2004.07.013.CrossRefPubMed Dorai T, Aggarwal BB: Role of chemopreventive agents in cancer therapy. Cancer Lett. 2004, 215: 129-140. 10.1016/j.canlet.2004.07.013.CrossRefPubMed
5.
go back to reference Ghersi D, Wilcken N, Simes RJ: A systematic review of taxane-containing regimens for metastatic breast cancer. Br J Cancer. 2005, 93: 293-301. 10.1038/sj.bjc.6602680.CrossRefPubMedPubMedCentral Ghersi D, Wilcken N, Simes RJ: A systematic review of taxane-containing regimens for metastatic breast cancer. Br J Cancer. 2005, 93: 293-301. 10.1038/sj.bjc.6602680.CrossRefPubMedPubMedCentral
6.
go back to reference Lopez-Lazaro M: Flavonoids as anticancer agents: structure-activity relationship study. Curr Med Chem Anti-Cancer Agents. 2002, 2: 691-714. 10.2174/1568011023353714.CrossRefPubMed Lopez-Lazaro M: Flavonoids as anticancer agents: structure-activity relationship study. Curr Med Chem Anti-Cancer Agents. 2002, 2: 691-714. 10.2174/1568011023353714.CrossRefPubMed
7.
go back to reference Surh YJ: Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer. 2003, 3: 768-780. 10.1038/nrc1189.CrossRefPubMed Surh YJ: Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer. 2003, 3: 768-780. 10.1038/nrc1189.CrossRefPubMed
8.
go back to reference Philip PA: Experience with docetaxel in the treatment of gastric cancer. Semin Oncol. 2005, 32: S24-38. 10.1053/j.seminoncol.2005.04.004.CrossRefPubMed Philip PA: Experience with docetaxel in the treatment of gastric cancer. Semin Oncol. 2005, 32: S24-38. 10.1053/j.seminoncol.2005.04.004.CrossRefPubMed
9.
go back to reference Chung KT, Wong TY, Wei CI, Huang YW, Lin Y: Tannins and human health: a review. Crit Rev Food Sci Nutr. 1998, 38: 421-464. 10.1080/10408699891274273.CrossRefPubMed Chung KT, Wong TY, Wei CI, Huang YW, Lin Y: Tannins and human health: a review. Crit Rev Food Sci Nutr. 1998, 38: 421-464. 10.1080/10408699891274273.CrossRefPubMed
10.
go back to reference Tang W, Hemm I, Bertram B: Recent development of antitumor agents from Chinese herbal medicines; Part I. Low molecular compounds. Planta Med. 2003, 69: 97-108. 10.1055/s-2003-37718.CrossRefPubMed Tang W, Hemm I, Bertram B: Recent development of antitumor agents from Chinese herbal medicines; Part I. Low molecular compounds. Planta Med. 2003, 69: 97-108. 10.1055/s-2003-37718.CrossRefPubMed
11.
go back to reference Kinghorn AD, Su BN, Jang DS, Chang LC, Lee D, Gu JQ, Carcache-Blanco EJ, Pawlus AD, Lee SK, Park EJ, Luendent M, Gills JJ, Bhat K, Park HS, Mata-Greenwoode E, Song LL, Jang M, Pezzuto JM: Natural Inhibitors of carcinogenesis. Planta Med. 2004, 70: 691-705. 10.1055/s-2004-827198.CrossRefPubMed Kinghorn AD, Su BN, Jang DS, Chang LC, Lee D, Gu JQ, Carcache-Blanco EJ, Pawlus AD, Lee SK, Park EJ, Luendent M, Gills JJ, Bhat K, Park HS, Mata-Greenwoode E, Song LL, Jang M, Pezzuto JM: Natural Inhibitors of carcinogenesis. Planta Med. 2004, 70: 691-705. 10.1055/s-2004-827198.CrossRefPubMed
12.
go back to reference Akihisa T, Yasukawa K, Oinuma H, Kasahara Y, Yamanouchi S, Takido M, Kumasi K, Tamura T: Triterpene alcohols from the flowers of compositae and their anti-inflammatory effects. Phytochemistry. 1996, 43: 1255-1260. 10.1016/S0031-9422(96)00343-3.CrossRefPubMed Akihisa T, Yasukawa K, Oinuma H, Kasahara Y, Yamanouchi S, Takido M, Kumasi K, Tamura T: Triterpene alcohols from the flowers of compositae and their anti-inflammatory effects. Phytochemistry. 1996, 43: 1255-1260. 10.1016/S0031-9422(96)00343-3.CrossRefPubMed
13.
go back to reference Della Logia R, Tubaro A, Sosa A, Becker H, Saar S, Isaac O: The role of triterpenoids in the topical anti-inflammatory activity of Calendula officinalis flowers. Planta Med. 1994, 60: 516-520.CrossRef Della Logia R, Tubaro A, Sosa A, Becker H, Saar S, Isaac O: The role of triterpenoids in the topical anti-inflammatory activity of Calendula officinalis flowers. Planta Med. 1994, 60: 516-520.CrossRef
14.
go back to reference Kalvatchev Z, Walder R, Garzaro D: Anti-HIV activity of extracts from Calendula officinalis flowers. Biomed Pharmacother. 1997, 51: 176-180. 10.1016/S0753-3322(97)85587-4.CrossRefPubMed Kalvatchev Z, Walder R, Garzaro D: Anti-HIV activity of extracts from Calendula officinalis flowers. Biomed Pharmacother. 1997, 51: 176-180. 10.1016/S0753-3322(97)85587-4.CrossRefPubMed
15.
go back to reference Perez-Carreon JI, Cruz-Jimenez G, Licea-Vega JA, Arce-Popoca E, Fattel-Fazenda S, Villa-Trevino S: Genotoxic and anti-genotoxic properties of Calendula officinalis extracts in rat liver cell cultures treated with diethylnitrosamine. Toxicol in Vitro. 2002, 16: 253-258. 10.1016/S0887-2333(02)00005-X.CrossRefPubMed Perez-Carreon JI, Cruz-Jimenez G, Licea-Vega JA, Arce-Popoca E, Fattel-Fazenda S, Villa-Trevino S: Genotoxic and anti-genotoxic properties of Calendula officinalis extracts in rat liver cell cultures treated with diethylnitrosamine. Toxicol in Vitro. 2002, 16: 253-258. 10.1016/S0887-2333(02)00005-X.CrossRefPubMed
16.
go back to reference Pommier P, Gomez F, Sunyach MP, D'Hombres A, Carrie C, Montbarbon X: Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol. 2004, 22: 1447-1453. 10.1200/JCO.2004.07.063.CrossRefPubMed Pommier P, Gomez F, Sunyach MP, D'Hombres A, Carrie C, Montbarbon X: Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol. 2004, 22: 1447-1453. 10.1200/JCO.2004.07.063.CrossRefPubMed
17.
go back to reference Boucaud-Maitre Y, Algernon O, Raynaud J: Cytotoxic and antitumoral activity of Calendula officinalis extracts. Pharmazie. 1988, 43: 220-221.PubMed Boucaud-Maitre Y, Algernon O, Raynaud J: Cytotoxic and antitumoral activity of Calendula officinalis extracts. Pharmazie. 1988, 43: 220-221.PubMed
18.
go back to reference Yoshikawa M, Murakami T, Kishi A, Kageura T, Matsuda H: Medicinal flowers. III. Marigold. (1): hypoglycemic, gastric emptying inhibitory, and gastroprotective principles and new oleanane-type triterpene oligoglycosides, calendasaponins A, B, C, and D, from Egyptian Calendula officinalis. Chem Pharm Bull. 2001, 49: 863-870. 10.1248/cpb.49.863.CrossRefPubMed Yoshikawa M, Murakami T, Kishi A, Kageura T, Matsuda H: Medicinal flowers. III. Marigold. (1): hypoglycemic, gastric emptying inhibitory, and gastroprotective principles and new oleanane-type triterpene oligoglycosides, calendasaponins A, B, C, and D, from Egyptian Calendula officinalis. Chem Pharm Bull. 2001, 49: 863-870. 10.1248/cpb.49.863.CrossRefPubMed
19.
go back to reference Neukirch H, D'Ambrosio M, Dall-Via J, Guerriero A: Simultaneous quantitative determination of eight triterpenoid monoesters from flowers of 10 varieties of Calendula officinalis L. and characterisation of a new triterpenoid monoester. Phytochem Anal. 2004, 15: 30-35. 10.1002/pca.739.CrossRefPubMed Neukirch H, D'Ambrosio M, Dall-Via J, Guerriero A: Simultaneous quantitative determination of eight triterpenoid monoesters from flowers of 10 varieties of Calendula officinalis L. and characterisation of a new triterpenoid monoester. Phytochem Anal. 2004, 15: 30-35. 10.1002/pca.739.CrossRefPubMed
20.
go back to reference Robertson MJ, Cochran KJ, Cameron C, Le JM, Tantravahi R, Ritz J: Characterization of a cell line, NKL, derived from an aggressive human natural killer cell leukemia. Exp Hematol. 1996, 24: 406-415.PubMed Robertson MJ, Cochran KJ, Cameron C, Le JM, Tantravahi R, Ritz J: Characterization of a cell line, NKL, derived from an aggressive human natural killer cell leukemia. Exp Hematol. 1996, 24: 406-415.PubMed
21.
go back to reference Liebmann JE, Cook JA, Lipschultz C, Teague D, Fisher J, Mitchell JB: Cytotoxic studies of paclitaxel (Taxol) in human tumour cell lines. Br J Cancer. 1993, 68: 1104-1109.CrossRefPubMedPubMedCentral Liebmann JE, Cook JA, Lipschultz C, Teague D, Fisher J, Mitchell JB: Cytotoxic studies of paclitaxel (Taxol) in human tumour cell lines. Br J Cancer. 1993, 68: 1104-1109.CrossRefPubMedPubMedCentral
22.
go back to reference Singh RP, Dhanalakshmi S, Agarwal R: Phytochemicals as cell cycle modulators: a less toxic approach in halting human cancers. Cell Cycle. 2002, 1: 156-161.CrossRefPubMed Singh RP, Dhanalakshmi S, Agarwal R: Phytochemicals as cell cycle modulators: a less toxic approach in halting human cancers. Cell Cycle. 2002, 1: 156-161.CrossRefPubMed
23.
24.
go back to reference Jo EH, Kim SH, Ra JC, Kim SR, Cho SD, Jung JW, Yang SR, Park JS, Hwang JW, Aruoma OI, Kim TY, Lee YS, Yang KS: Chemopreventive properties of the ethanol extract of Chinese licorice (Glycyrrhiza uralensis) root: induction of apoptosis and G1 cell cycle arrest in MCF-7 human breast cancer cells. Cancer Lett. 2005, 230: 239-247. 10.1016/j.canlet.2004.12.038.CrossRefPubMed Jo EH, Kim SH, Ra JC, Kim SR, Cho SD, Jung JW, Yang SR, Park JS, Hwang JW, Aruoma OI, Kim TY, Lee YS, Yang KS: Chemopreventive properties of the ethanol extract of Chinese licorice (Glycyrrhiza uralensis) root: induction of apoptosis and G1 cell cycle arrest in MCF-7 human breast cancer cells. Cancer Lett. 2005, 230: 239-247. 10.1016/j.canlet.2004.12.038.CrossRefPubMed
25.
go back to reference Kundu T, Dey S, Roy M, Siddiqui M, Bhattachrya RK: Induction of apoptosis in human leukaemia cells by black tea and its polyphenol theaflavin. Cancer Lett. 2005, 230: 111-121. 10.1016/j.canlet.2004.12.035.CrossRefPubMed Kundu T, Dey S, Roy M, Siddiqui M, Bhattachrya RK: Induction of apoptosis in human leukaemia cells by black tea and its polyphenol theaflavin. Cancer Lett. 2005, 230: 111-121. 10.1016/j.canlet.2004.12.035.CrossRefPubMed
26.
go back to reference Garcia-Lora A, Pedrinaci S, Garrido F: Protein-bound polysaccharide K and interleukin-2 regulate different nuclear transcription factors in the NKL human natural killer cell line. Cancer Immunol Immunother. 2001, 50: 191-198. 10.1007/s002620100189.CrossRefPubMed Garcia-Lora A, Pedrinaci S, Garrido F: Protein-bound polysaccharide K and interleukin-2 regulate different nuclear transcription factors in the NKL human natural killer cell line. Cancer Immunol Immunother. 2001, 50: 191-198. 10.1007/s002620100189.CrossRefPubMed
27.
go back to reference Kudo S, Tanaka J, Kashida H, Tamegai Y, Endo S, Yamano HO: Effectiveness of immunochemotherapy with PSK, a protein-bound polysaccharide, in colorectal cancer and changes of tumor marker. Oncol Rep. 2002, 9: 635-638.PubMed Kudo S, Tanaka J, Kashida H, Tamegai Y, Endo S, Yamano HO: Effectiveness of immunochemotherapy with PSK, a protein-bound polysaccharide, in colorectal cancer and changes of tumor marker. Oncol Rep. 2002, 9: 635-638.PubMed
28.
go back to reference Ohwada S, Ikeya T, Yokomori T, Kusaba T, Roppongi T, Takahashi T, Nakamura S, Kakinuma S, Iwazaki S, Ishikawa H, Kawate S, Nakajima T, Morishita Y: Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer: a randomised controlled study. Br J Cancer. 2004, 90: 1003-1010. 10.1038/sj.bjc.6601619.CrossRefPubMedPubMedCentral Ohwada S, Ikeya T, Yokomori T, Kusaba T, Roppongi T, Takahashi T, Nakamura S, Kakinuma S, Iwazaki S, Ishikawa H, Kawate S, Nakajima T, Morishita Y: Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer: a randomised controlled study. Br J Cancer. 2004, 90: 1003-1010. 10.1038/sj.bjc.6601619.CrossRefPubMedPubMedCentral
29.
go back to reference Kariya Y, Inoue N, Kihara T, Fujii M: Activation of human natural killer cells by the protein bound polysaccharide PSK independently of interferon and interleukin 2. Immunol Lett. 1992, 31: 241-245. 10.1016/0165-2478(92)90121-4.CrossRefPubMed Kariya Y, Inoue N, Kihara T, Fujii M: Activation of human natural killer cells by the protein bound polysaccharide PSK independently of interferon and interleukin 2. Immunol Lett. 1992, 31: 241-245. 10.1016/0165-2478(92)90121-4.CrossRefPubMed
30.
go back to reference Algarra I, Collado A, Garcia-Lora A, Garrido F: Differential effect of protein-bound polysaccharide (PSK) on survival of experimental murine tumors. J Exp Clin Cancer Res. 1999, 18: 39-46.PubMed Algarra I, Collado A, Garcia-Lora A, Garrido F: Differential effect of protein-bound polysaccharide (PSK) on survival of experimental murine tumors. J Exp Clin Cancer Res. 1999, 18: 39-46.PubMed
31.
go back to reference Smyth MJ, Crowe NY, Hayakawa Y, Takeda K, Yagita H, Godfrey DI: NKT cells – conductors of tumor immunity?. Curr Opin Immunol. 2002, 14: 165-171. 10.1016/S0952-7915(02)00316-3.CrossRefPubMed Smyth MJ, Crowe NY, Hayakawa Y, Takeda K, Yagita H, Godfrey DI: NKT cells – conductors of tumor immunity?. Curr Opin Immunol. 2002, 14: 165-171. 10.1016/S0952-7915(02)00316-3.CrossRefPubMed
32.
go back to reference Crowe NY, Smyth MJ, Godfrey DI: A critical role for natural killer T cells in immunosurveillance of methylcholanthrene-induced sarcomas. J Exp Med. 2002, 196: 119-127. 10.1084/jem.20020092.CrossRefPubMedPubMedCentral Crowe NY, Smyth MJ, Godfrey DI: A critical role for natural killer T cells in immunosurveillance of methylcholanthrene-induced sarcomas. J Exp Med. 2002, 196: 119-127. 10.1084/jem.20020092.CrossRefPubMedPubMedCentral
Metadata
Title
A new extract of the plant calendula officinalis produces a dual in vitroeffect: cytotoxic anti-tumor activity and lymphocyte activation
Authors
Eva Jiménez-Medina
Angel Garcia-Lora
Laura Paco
Ignacio Algarra
Antonia Collado
Federico Garrido
Publication date
01-12-2006
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2006
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-6-119

Other articles of this Issue 1/2006

BMC Cancer 1/2006 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine