Carnosic Acid Inhibits the Proliferation and Migration Capacity of Human Colorectal Cancer Cells

Overview

Journal Oncol Rep

Specialty Oncology

Date 2012 Jan 17

PMID 22246562

Citations 35

Authors

M V Barni

M J Carlini

E G Cafferata

L Puricelli

S Moreno

Affiliations

Soon will be listed here.

Abstract

Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide. The objective of this study was to examine whether carnosic acid (CA), the main antioxidant compound of Rosmarinus officinalis L., would inhibit the cell viability of three CRC cell lines: Caco-2, HT29 and LoVo in a dose-dependent manner, with IC₅₀ values in the range of 24-96 µM. CA induced cell death by apoptosis in Caco-2 line after 24 h of treatment and inhibited cell adhesion and migration, possibly by reducing the activity of secreted proteases such as urokinase plasminogen activator (uPA) and metalloproteinases (MMPs). These effects may be associated through a mechanism involving the inhibition of the COX-2 pathway, because we have determined that CA downregulates the expression of COX-2 in Caco-2 cells at both the mRNA and protein levels. Therefore, CA modulates different targets involved in the development of CRC. These findings indicate that carnosic acid may have anticancer activity and may be useful as a novel chemotherapeutic agent.

Citing Articles

Sustainable biosynthesis of valuable diterpenes in microbes.

Liu Y, Chen X, Zhang C Eng Microbiol. 2024; 3(1):100058.

PMID: 39628524 PMC: 11611012. DOI: 10.1016/j.engmic.2022.100058.

Molecular and circuit determinants in the globus pallidus mediating control of cocaine-induced behavioral plasticity.

Tian G, Bartas K, Hui M, Chen L, Vasquez J, Azouz G Neuron. 2024; 112(20):3470-3485.e12.

PMID: 39153478 PMC: 11502257. DOI: 10.1016/j.neuron.2024.07.018.

Carnosic Acid against Lung Cancer: Induction of Autophagy and Activation of Sestrin-2/LKB1/AMPK Signalling.

ONeill E, Sze N, MacPherson R, Tsiani E Int J Mol Sci. 2024; 25(4).

PMID: 38396629 PMC: 10888478. DOI: 10.3390/ijms25041950.

Carnosic acid nanocluster-based framework combined with PD-1 inhibitors impeded tumorigenesis and enhanced immunotherapy in hepatocellular carcinoma.

Wu W, Li Y, Wu X, Liang J, You W, He X Funct Integr Genomics. 2024; 24(1):5.

PMID: 38182693 DOI: 10.1007/s10142-024-01286-2.

Pro-Apoptotic Activity and Cell Cycle Arrest of against SKLU-1 Cancer Cell in 2D and 3D Cultures.

Agena R, Cortes-Sanchez A, Hernandez-Sanchez H, Alvarez-Salas L, Martinez-Rodriguez O, Garcia V Molecules. 2023; 28(11).

PMID: 37298837 PMC: 10254354. DOI: 10.3390/molecules28114361.

References

Friedl P, Wolf K . Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer. 2003; 3(5):362-74. DOI: 10.1038/nrc1075. View

Lim Y, Park H, Hwang H, Kang S, Pyun J, Lee M . (-)-Epigallocatechin-3-gallate (EGCG) inhibits HGF-induced invasion and metastasis in hypopharyngeal carcinoma cells. Cancer Lett. 2008; 271(1):140-52. DOI: 10.1016/j.canlet.2008.05.048. View

Storz P . Reactive oxygen species in tumor progression. Front Biosci. 2005; 10:1881-96. DOI: 10.2741/1667. View

Yu Y, Lin C, Chan H, Tsai H . Carnosic acid reduces cytokine-induced adhesion molecules expression and monocyte adhesion to endothelial cells. Eur J Nutr. 2009; 48(2):101-6. DOI: 10.1007/s00394-008-0768-x. View

Mengoni E, Vichera G, Rigano L, Rodriguez-Puebla M, Galliano S, Cafferata E . Suppression of COX-2, IL-1β and TNF-α expression and leukocyte infiltration in inflamed skin by bioactive compounds from Rosmarinus officinalis L. Fitoterapia. 2010; 82(3):414-21. DOI: 10.1016/j.fitote.2010.11.023. View

Steiner M, Priel I, Giat J, Levy J, Sharoni Y, Danilenko M . Carnosic acid inhibits proliferation and augments differentiation of human leukemic cells induced by 1,25-dihydroxyvitamin D3 and retinoic acid. Nutr Cancer. 2002; 41(1-2):135-44. DOI: 10.1080/01635581.2001.9680624. View

Huang S, Zheng R . Rosmarinic acid inhibits angiogenesis and its mechanism of action in vitro. Cancer Lett. 2005; 239(2):271-80. DOI: 10.1016/j.canlet.2005.08.025. View

Lee K, Bode A, Dong Z . Molecular targets of phytochemicals for cancer prevention. Nat Rev Cancer. 2011; 11(3):211-8. DOI: 10.1038/nrc3017. View

Cao Y, Prescott S . Many actions of cyclooxygenase-2 in cellular dynamics and in cancer. J Cell Physiol. 2002; 190(3):279-86. DOI: 10.1002/jcp.10068. View

10.

Philip M, Rowley D, Schreiber H . Inflammation as a tumor promoter in cancer induction. Semin Cancer Biol. 2004; 14(6):433-9. DOI: 10.1016/j.semcancer.2004.06.006. View

11.

Aggarwal B, Shishodia S . Suppression of the nuclear factor-kappaB activation pathway by spice-derived phytochemicals: reasoning for seasoning. Ann N Y Acad Sci. 2005; 1030:434-41. DOI: 10.1196/annals.1329.054. View

12.

Gupta R, DuBois R . Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer. 2002; 1(1):11-21. DOI: 10.1038/35094017. View

13.

Danilenko M, Wang Q, Wang X, Levy J, Sharoni Y, Studzinski G . Carnosic acid potentiates the antioxidant and prodifferentiation effects of 1alpha,25-dihydroxyvitamin D3 in leukemia cells but does not promote elevation of basal levels of intracellular calcium. Cancer Res. 2003; 63(6):1325-32. View

14.

Kundu J, Surh Y . Epigallocatechin gallate inhibits phorbol ester-induced activation of NF-kappa B and CREB in mouse skin: role of p38 MAPK. Ann N Y Acad Sci. 2007; 1095:504-12. DOI: 10.1196/annals.1397.054. View

15.

Tsujii M, Kawano S, DuBois R . Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci U S A. 1997; 94(7):3336-40. PMC: 20370. DOI: 10.1073/pnas.94.7.3336. View

16.

Park C, Moon D, Choi I, Choi B, Nam T, Rhu C . Curcumin induces apoptosis and inhibits prostaglandin E(2) production in synovial fibroblasts of patients with rheumatoid arthritis. Int J Mol Med. 2007; 20(3):365-72. View

17.

Sobolewski C, Cerella C, Dicato M, Ghibelli L, Diederich M . The role of cyclooxygenase-2 in cell proliferation and cell death in human malignancies. Int J Cell Biol. 2010; 2010:215158. PMC: 2841246. DOI: 10.1155/2010/215158. View

18.

Bruce W, Giacca A, Medline A . Possible mechanisms relating diet and risk of colon cancer. Cancer Epidemiol Biomarkers Prev. 2001; 9(12):1271-9. View

19.

Aguirre Ghiso J, Farias E, Alonso D, Joffe E . Secretion of urokinase and metalloproteinase-9 induced by staurosporine is dependent on a tyrosine kinase pathway in mammary tumor cells. Int J Cancer. 1998; 76(3):362-7. DOI: 10.1002/(sici)1097-0215(19980504)76:3<362::aid-ijc13>3.0.co;2-d. View

20.

Lai K, Huang A, Hsu S, Kuo C, Yang J, Wu S . Benzyl isothiocyanate (BITC) inhibits migration and invasion of human colon cancer HT29 cells by inhibiting matrix metalloproteinase-2/-9 and urokinase plasminogen (uPA) through PKC and MAPK signaling pathway. J Agric Food Chem. 2010; 58(5):2935-42. DOI: 10.1021/jf9036694. View