Anti-metastatic activity of curcumin and catechin
Introduction
Metastasis of cancer cells to distant sites is one of the major deciding factors in cancer outcome. In fact, prognosis of cancer is mainly determined by the invasiveness of the tumour and its ability to metastasize. Although there are several drugs available to control cancer growth in humans, there are no drugs presently available to specifically inhibit the metastasis of cancer cells.
There is a cascade of events leading to the metastasis of tumours [1], [2]. These include separation from the primary site, circulation through blood or lymph, adhesion to the basement membrane, invasion and proliferation at distant sites [3]. Any drug which can inhibit one of the steps in the cascade will be useful in the inhibition of tumour metastasis.
Proteolytic degradation of the basement membrane is a major step in the metastasis leading to invasion [4], [5]. Curcumin, isolated from Curcuma longa, a non-steroidal polyphenol, has been found to produce lysosomal integrity and inhibit proteolysis [6], [7]. Similarly catechin, a naturally occurring polyphenol was found to make stable cross-links with collagen [8], and the catechin–collagen complex was found to be non-susceptible to mammalian collagenase in vitro [9].
We previously reported the anti-metastatic activity of several polyphenols, including catechin and curcumin, on B16F-10 melanoma cells in mice [10]. In the present report, we report the mechanism of action of the compounds using in vitro and in vivo models.
Section snippets
Animals
C57BL/6 mice were obtained from the National Centre for Laboratory Animal Sciences (NCLAS), National Institute of Nutrition (Hiderabad, India), and were housed in ventilated cages. The animals were fed with mouse chow (Lipton, India) and water ad libitum throughout the experimental period.
Tumour cell line
B16F-10 melanoma cells were obtained from the National Facility for Animal Tissue and Cell Culture (Pune, India) and were maintained in tissue culture using DMEM supplemented with 10% FCS l-glutamine and
Effect of curcumin and catechin on the inhibition of lung metastasis and survival
The effects of curcumin and catechin on the inhibition of lung metastasis are given in Table 1. Curcumin- and catechin-treated animals had a significant reduction in the number of lung tumour nodules. The untreated control tumour-bearing animals had massive lung tumour nodules and were assigned the number of nodules as 250 [17]. The compounds curcumin and catechin significantly reduced the lung tumour nodules (89.3% and 82.2%, respectively) compared to the control metastatic tumour-bearing
Discussion
The results presented in this study show that curcumin and catechin can effectively inhibit metastases induced by B16F-10 melanoma cells, and that this may be due to inhibition of metalloproteinases. Metalloproteinases have been implicated in the denaturation of the basement membrane during the metastatic invasion of tumour cells [5], [18]. The results presented in this study indicate that curcumin and catechin could inhibit the action of metalloproteinases in vitro, as seen from the
Acknowledgements
The authors are grateful to the Council of Scientific and Industrial Research, New Delhi, India for funding this project.
References (30)
Proteolytic remodelling of extra-cellular matrix
Curr. Opin. Cell Biol.
(1995)Biochem. Pharmacol.
(1971)- et al.
Inhibition of lung metastasis in mice induced by B16F-10 melanoma cells by polyphenolic compounds
Cancer Lett.
(1995) - et al.
The determination of hydroxyproline in urine hydrolysates
Clin. Chim. Acta
(1970) Antioxidant activity of curcumin and related compounds
Biochem. Pharmacol.
(1976)- et al.
Inhibition of chemical carcinogenesis by curcumin
J. Ethnopharmacol.
(1989) - et al.
Green tea and skin – anticarcinogenic effects
J. Invest. Dermatol.
(1994) - et al.
The pathogenesis of cancer metastasis
Nature (London)
(1980) - et al.
The biology of cancer invasion and metastasis
Adv. Cancer Res.
(1978) - et al.
Cancer invasion and metastasis
Q. Rev. Biol.
(1980)
Proteolytic degradation of extracellular matrix in tumour invasion
Biochim. Biophys. Acta
J. Pharmacol. Exp. Ther.
Collagen treated (+)-catechin becomes resistant to the action of mammalian collagenase
Experientia
General consideration for studies of experimental cancer metastasis
Methods Cancer Res.
Cited by (174)
Therapeutic potential and limitations of curcumin as antimetastatic agent
2023, Biomedicine and PharmacotherapyDevelopment of water-dispersible gelatin stabilized hydroxyapatite nanoformulation for curcumin delivery
2021, Journal of Drug Delivery Science and TechnologyThe therapeutic potential of curcumin in alleviating N-diethylnitrosamine and iron nitrilotriacetate induced renal cell tumours in mice via inhibition of oxidative stress: Implications for cancer chemoprevention
2021, Biomedicine and PharmacotherapyCitation Excerpt :In vivo, turmeric also suppresses chemically induced carcinogenesis of the forestomach [30], azoxymethane-induced tumour in rat colon [31], suppress mammary and hepatic carcinogenesis etc [32,33]. Curcumin also possesses an antimetastatic activity [34]. However, anticarcinogenic and antimetastatic effects of curcumin are not fully understood, but it has been shown to inhibit the development of human umbilical vein endothelial cells [35], oppress angiogenesis in vivo [36], inhibit angiogenic response stimulated by growth factor-2, including matrix expression of metalloprotease gelatinase. [37],
Application of nano/microencapsulated phenolic compounds against cancer
2020, Advances in Colloid and Interface Science