Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2017

Open Access 01-12-2017 | Research article

Extract of Ginkgo biloba exacerbates liver metastasis in a mouse colon cancer Xenograft model

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

Login to get access

Abstract

Background

Metastasis refers to the spread of a primary tumor cell from the primary site to other locations in the body and it is generally associated with the severity of a tumor. Extract of Ginkgo biloba (EGb) contains various bioactive compounds and it exerts beneficial effects including improvements in brain function and reduced risk of cardiovascular diseases. On the other hand, increased risk of thyroid and liver cancers by EGb have been reported in animals.

Methods

A colon cancer metastasis model was established using intrasplenic injection of a human colon cancer cell line, SW620-luc in athymic mice to investigate the potential impact of EGb on colon cancer progression. After tumor establishment, EGb was intraperitonically injected daily for 5 wks.

Results

EGb significantly increased the rate of metastasis in mouse liver and decreased the number of necrotic and apoptotic cells in the metastatic liver when compared to the control. Meanwhile, EGb significantly induced proliferation of tumor cells in the metastatic liver, indicated by increased staining of Ki67 and H3S10p. mRNA expression of genes involved in cell cycle, metastasis, apoptosis, and oxidative stress were altered by EGb treatment in livers with tumors. Moreover, EGb activated the stress-responsive MAPK pathways in the liver with metastatic tumors.

Conclusions

EGb exacerbated liver metastasis in a mouse colon cancer metastasis model. This is potentially due to the increased tumor cell proliferation involving stimulated MAPK pathways.
Appendix
Available only for authorised users
Literature
1.
Abdalla EK, Adam R, Bilchik AJ, Jaeck D, Vauthey JN, Mahvi D. Improving resectability of hepatic colorectal metastases: expert consensus statement. Ann Surg Oncol. 2006;13(10):1271–80.CrossRefPubMed
2.
3.
van Beek TA, Montoro P. Chemical analysis and quality control of Ginkgo Biloba leaves, extracts, and phytopharmaceuticals. J Chromatogr A. 2009;1216(11):2002–32.CrossRefPubMed
4.
McKenna DJ, Jones K, Hughes K. Efficacy, safety, and use of ginkgo biloba in clinical and preclinical applications. Altern Ther Health Med. 2001;7(5):70–86. 88-90PubMed
5.
Mohanta TK, Tamboli Y, Zubaidha PK. Phytochemical and medicinal importance of Ginkgo Biloba L. Nat Prod Res. 2014;28(10):746–52.CrossRefPubMed
6.
Zhou LX, Zhu Y. Influence of Ginkgo Biloba extract on the proliferation, apoptosis of ACC-2 cell and Survivin gene expression in adenoid cystic carcinoma of lacrimal gland. Asian Pac J Trop Med. 2012;5(11):897–900.CrossRefPubMed
7.
Moon YJ, Wang X, Morris ME. Dietary flavonoids: effects on xenobiotic and carcinogen metabolism. Toxicol in Vitro. 2006;20(2):187–210.CrossRefPubMed
8.
Chan PC, Xia Q, Fu PP. Ginkgo Biloba leave extract: biological, medicinal, and toxicological effects. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2007;25(3):211–44.CrossRefPubMed
9.
Le Bars PL, Katz MM, Berman N, Itil TM, Freedman AM, Schatzberg AF. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo Biloba for dementia. North American EGb Study Group. JAMA. 1997;278(16):1327–32.CrossRefPubMed
10.
Gardner CD, Zehnder JL, Rigby AJ, Nicholus JR, Farquhar JW. Effect of Ginkgo Biloba (EGb 761) and aspirin on platelet aggregation and platelet function analysis among older adults at risk of cardiovascular disease: a randomized clinical trial. Blood Coagul Fibrinolysis. 2007;18(8):787–93.CrossRefPubMed
11.
Papadopoulos V, Kapsis A, Li H, Amri H, Hardwick M, Culty M, Kasprzyk PG, Carlson M, Moreau JP, Drieu K. Drug-induced inhibition of the peripheral-type benzodiazepine receptor expression and cell proliferation in human breast cancer cells. Anticancer Res. 2000;20(5A):2835–47.PubMed
12.
Gohil K, Moy RK, Farzin S, Maguire JJ, Packer L. mRNA expression profile of a human cancer cell line in response to Ginkgo Biloba extract: induction of antioxidant response and the Golgi system. Free Radic Res. 2000;33(6):831–49.CrossRefPubMed
13.
Ao Q, Sun XH, Wang AJ, Fu PF, Gong K, Zuo HC, Gong YD, Zhang XF. Protective effects of extract of Ginkgo Biloba (EGb 761) on nerve cells after spinal cord injury in rats. Spinal Cord. 2006;44(11):662–7.CrossRefPubMed
14.
Ergun U, Yurtcu E, Ergun MA. Protective effect of ginkgo biloba against gossypol-induced apoptosis in human lymphocytes. Cell Biol Int. 2005;29(8):717–20.CrossRefPubMed
15.
Schindowski K, Leutner S, Kressmann S, Eckert A, Muller WE. Age-related increase of oxidative stress-induced apoptosis in mice prevention by Ginkgo Biloba extract (EGb761). J Neural Transm. 2001;108(8–9):969–78.CrossRefPubMed
16.
Tian YM, Tian HJ, Zhang GY, Dai YR. Effects of Ginkgo Biloba extract (EGb 761) on hydroxyl radical-induced thymocyte apoptosis and on age-related thymic atrophy and peripheral immune dysfunctions in mice. Mech Ageing Dev. 2003;124(8–9):977–83.CrossRefPubMed
17.
Sastre J, Millan A. Garcia de la Asuncion J, Pla R, Juan G, Pallardo, O'Connor E, Martin JA, Droy-Lefaix MT, Vina J: a Ginkgo Biloba extract (EGb 761) prevents mitochondrial aging by protecting against oxidative stress. Free Radic Biol Med. 1998;24(2):298–304.CrossRefPubMed
18.
19.
Shi C, Xiao S, Liu J, Guo K, Wu F, Yew DT, Xu J. Ginkgo Biloba extract EGb761 protects against aging-associated mitochondrial dysfunction in platelets and hippocampi of SAMP8 mice. Platelets. 2010;21(5):373–9.CrossRefPubMed
20.
Nevado J, Sanz R, Sanchez-Rodriguez C, Garcia-Berrocal JR, Martin-Sanz E, Gonzalez-Garcia JA, Esteban-Sanchez J, Ramirez-Camacho R. Ginkgo Biloba extract (EGb761) protects against aging-related caspase-mediated apoptosis in rat cochlea. Acta Otolaryngol. 2010;130(10):1101–12.CrossRefPubMed
21.
Xin W, Wei T, Chen C, Ni Y, Zhao B, Hou J. Mechanisms of apoptosis in rat cerebellar granule cells induced by hydroxyl radicals and the effects of EGb761 and its constituents. Toxicology. 2000;148(2–3):103–10.CrossRefPubMed
22.
Smith JV, Burdick AJ, Golik P, Khan I, Wallace D, Luo Y. Anti-apoptotic properties of Ginkgo Biloba extract EGb 761 in differentiated PC12 cells. Cell Mol Biol (Noisy-le-grand). 2002;48(6):699–707.
23.
Mak YT, Chan WY, Lam WP, Yew DT. Immunohistological evidences of Ginkgo Biloba extract altering Bax to Bcl-2 expression ratio in the hippocampus and motor cortex of senescence accelerated mice. Microsc Res Tech. 2006;69(8):601–5.CrossRefPubMed
24.
Kang X, Chen J, Xu Z, Li H, Wang B. Protective effects of Ginkgo Biloba extract on paraquat-induced apoptosis of PC12 cells. Toxicol in Vitro. 2007;21(6):1003–9.CrossRefPubMed
25.
Koh PO. Gingko Biloba extract (EGb 761) prevents increase of bad-Bcl-XL interaction following cerebral ischemia. Am J Chin Med. 2009;37(5):867–76.CrossRefPubMed
26.
Li S, Tang D, Xue Z, Zhang Z, Sun X, Liu Y, Dong H, Yin X, Zhang Z. Biphasic effect of EGb761 on simulated ischemia-induced rat BMSC survival in vitro and in vivo. Life Sci. 2011;88(19–20):853–63.CrossRefPubMed
27.
Massieu L, Moran J, Christen Y. Effect of Ginkgo Biloba (EGb 761) on staurosporine-induced neuronal death and caspase activity in cortical cultured neurons. Brain Res. 2004;1002(1–2):76–85.CrossRefPubMed
28.
Ren DC, Du GH, Zhang JT. Protective effect of ginkgo biloba extract on endothelial cell against damage induced by oxidative stress. J Cardiovasc Pharmacol. 2002;40(6):809–14.CrossRefPubMed
29.
Coskun O, Armutcu F, Kanter M, Kuzey GM. Protection of endotoxin-induced oxidative renal tissue damage of rats by vitamin E or/and EGb 761 treatment. J Appl Toxicol. 2005;25(1):8–12.CrossRefPubMed
30.
Liu XP, Goldring CE, Wang HY, Copple IM, Kitteringham NR, Park BK, Wei W. Extract of Ginkgo Biloba induces glutamate cysteine ligase catalytic subunit (GCLC). Phytother Res. 2008;22(3):367–71.CrossRefPubMed
31.
Shah ZA, Nada SE, Dore S. Heme oxygenase 1, beneficial role in permanent ischemic stroke and in Gingko Biloba (EGb 761) neuroprotection. Neuroscience. 2011;180:248–55.CrossRefPubMedPubMedCentral
32.
Biggs ML, Sorkin BC, Nahin RL, Kuller LH, Fitzpatrick AL. Ginkgo Biloba and risk of cancer: secondary analysis of the ginkgo evaluation of memory (GEM) study. Pharmacoepidemiol Drug Saf. 2010;19(7):694–8.CrossRefPubMedPubMedCentral
33.
National Toxicology Program (U.S.). NTP technical report on the toxicology and carcinogenesis studies of Ginkgo biloba extract (CAS no. 90045–36-6) in F344/N rats and B6C3F1/N mice (gavage studies). Research Triangle Park, NC: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, National Toxicology Program; 2013.
34.
35.
Rojas P, Serrano-Garcia N, Mares-Samano JJ, Medina-Campos ON, Pedraza-Chaverri J, Ogren SO. EGb761 protects against nigrostriatal dopaminergic neurotoxicity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice: role of oxidative stress. Eur J Neurosci. 2008;28(1):41–50.CrossRefPubMed
36.
Hoenerhoff MJ, Pandiri AR, Snyder SA, Hong HH, Ton TV, Peddada S, Shockley K, Witt K, Chan P, Rider C, et al. Hepatocellular carcinomas in B6C3F1 mice treated with Ginkgo Biloba extract for two years differ from spontaneous liver tumors in cancer gene mutations and genomic pathways. Toxicol Pathol. 2013;41(6):826–41.CrossRefPubMed
37.
Turusov VS, Torii M, Sills RC, Willson GA, Herbert RA, Hailey JR, Haseman JK, Boorman GA. Hepatoblastomas in mice in the US National Toxicology Program (NTP) studies. Toxicol Pathol. 2002;30(5):580–91.CrossRefPubMed
38.
Dunnick JK, Hailey JR. Toxicity and carcinogenicity studies of quercetin, a natural component of foods. Fundam Appl Toxicol. 1992;19(3):423–31.CrossRefPubMed
39.
Harwood M, Danielewska-Nikiel B, Borzelleca JF, Flamm GW, Williams GM, Lines TC. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem Toxicol. 2007;45(11):2179–205.CrossRefPubMed
40.
Hard GC, Seely JC, Betz LJ, Hayashi SM. Re-evaluation of the kidney tumors and renal histopathology occurring in a 2-year rat carcinogenicity bioassay of quercetin. Food Chem Toxicol. 2007;45(4):600–8.CrossRefPubMed
41.
Guo L, Mei N, Liao W, Chan PC, Fu PP. Ginkgo Biloba extract induces gene expression changes in xenobiotics metabolism and the Myc-centered network. OMICS. 2010;14(1):75–90.CrossRefPubMedPubMedCentral
42.
Li Q, Chen H. Transcriptional silencing of N-Myc downstream-regulated gene 1 (NDRG1) in metastatic colon cancer cell line SW620. Clin ExpMetastasis. 2011;28(2):127–35.
43.
Murakami Y, Watari K, Shibata T, Uba M, Ureshino H, Kawahara A, Abe H, Izumi H, Mukaida N, Kuwano M, et al. N-myc downstream-regulated gene 1 promotes tumor inflammatory angiogenesis through JNK activation and autocrine loop of interleukin-1alpha by human gastric cancer cells. J Biol Chem. 2013;288(35):25025–37.CrossRefPubMedPubMedCentral
44.
Hamzawy M, Elsaid L, Shams A, Rashid L, Mahfouz S, Sharawy N. Study of the effects of cyclooxygenase-2 inhibitor on the promotion of hepatic tumorigenesis in rats fed a high fat diet. J Clin Exp Hepatol. 2015;5(1):14–21.CrossRefPubMedPubMedCentral
45.
Hsieh PS, Jin JS, Chiang CF, Chan PC, Chen CH, Shih KC. COX-2-mediated inflammation in fat is crucial for obesity-linked insulin resistance and fatty liver. Obesity (Silver Spring). 2009;17(6):1150–7.
46.
Sun Y, Chen J, Rigas B. Chemopreventive agents induce oxidative stress in cancer cells leading to COX-2 overexpression and COX-2-independent cell death. Carcinogenesis. 2009;30(1):93–100.CrossRefPubMed
47.
Wiesenauer CA, Yip-Schneider MT, Wang Y, Schmidt CM. Multiple anticancer effects of blocking MEK-ERK signaling in hepatocellular carcinoma. J Am Coll Surg. 2004;198(3):410–21.CrossRefPubMed
48.
Kim GY, Mercer SE, Ewton DZ, Yan Z, Jin K, Friedman E. The stress-activated protein kinases p38 alpha and JNK1 stabilize p21(Cip1) by phosphorylation. J Biol Chem. 2002;277(33):29792–802.CrossRefPubMed
49.
Wang Y, Wang R, Wang Y, Peng R, Wu Y, Yuan Y. Ginkgo Biloba extract mitigates liver fibrosis and apoptosis by regulating p38 MAPK, NF-kappaB/IkappaBalpha, and Bcl-2/Bax signaling. Drug Des Devel Ther. 2015;9:6303–17.PubMedPubMedCentral
50.
Lee P, Linderman JD, Smith S, Brychta RJ, Wang J, Idelson C, Perron RM, Werner CD, Phan GQ, Kammula US, et al. Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab. 2014;19(2):302–9.CrossRefPubMed
51.
Wang HW, Wu T, Qi JY, Wang YQ, Luo XP, Ning Q. Salidroside attenuates LPS-stimulated activation of THP-1 cell-derived macrophages through down-regulation of MAPK/NF-kB signaling pathways. J Huazhong Univ Sci Technolog Med Sci. 2013;33(4):463–9.CrossRefPubMed
Metadata
Title
Extract of Ginkgo biloba exacerbates liver metastasis in a mouse colon cancer Xenograft model
Publication date
01-12-2017
Published in
BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-017-2014-7

Other articles of this Issue 1/2017

BMC Complementary Medicine and Therapies 1/2017 Go to the issue

Research article

Predicting adherence to acupuncture appointments for low back pain: a prospective observational study

Research article

Probiotic mixture improves fatty liver disease by virtue of its action on lipid profiles, leptin, and inflammatory biomarkers

Correction

Correction to: Moon phases and Moon signs do not influence morbidity, mortality and long-term survival, after living donor kidney transplantation

Research article

Bacopa monnieri extract increases rat coronary flow and protects against myocardial ischemia/reperfusion injury

Research article

The treatment of migraine patients within chiropractic: analysis of a nationally representative survey of 1869 chiropractors

Research article

In vivo evaluation of hot water extract of Acorus gramineus root against benign prostatic hyperplasia