Cancer Letters

Cancer Letters

Volume 141, Issues 1–2, 1 July 1999, Pages 159-165
Cancer Letters

Anti-metastatic activity of curcumin and catechin

https://doi.org/10.1016/S0304-3835(99)00098-1Get rights and content

Abstract

The inhibitory effects of curcumin and catechin on lung metastasis induced by B16F-10 melanoma cells were studied in female C57BL/6 mice. Curcumin and catechin significantly (P<0.001) inhibited lung tumour formation (89.3% and 82.2%, respectively) and significantly increased the life span (143.9% and 80.8%, respectively). Moreover, lung collagen hydroxyproline and serum sialic acid levels were found to be significantly (P<0.001) lower in treated animals compared to the untreated controls. Curcumin and catechin treatment (10 μg/ml) significantly inhibited the invasion of B16F-10 melanoma cells across the collagen matrix of the Boyden chamber. Gelatin zymographic analysis of the trypsin-activated B16F-10 melanoma cells sonicate revealed that curcumin- and catechin-treated zymograms did not show any metalloproteinase activity. Curcumin and catechin treatment did not inhibit the motility of B16F-10 melanoma cells across a polycarbonate filter in vitro. These findings suggest that curcumin and catechin inhibit the invasion of B16F-10 melanoma cells by inhibition of metalloproteinases, thereby inhibiting lung metastasis.

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.

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