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Combination of curcuma zedoary and Kelp inhibits growth and metastasis of liver cancer in vivo and in vitro via reducing endogenous H2S level

Abstract

Compatibility of traditional Chinese medicine can improve efficacy for cancer treatment. Furthermore, combination of Traditional Chinese Medicine curcuma zedoary and Kelp is used to enhance the effect of the dissipation in a medical work of pediatrics in the Song Dynasty. Curcumenol and laminarin, main components from curcuma zedoary and Kelp, are also reported to have a wide range of biological activities. Therefore, we hypothesize that combination of curcuma zedoary and Kelp may prevent the development of cancer. The aim of this research was to confirm whether a combination of curcuma zedoary and Kelp could inhibit the proliferation and metastasis of hepatoma cells and consequently improve prognosis. In this study, we firstly found that the combination of curcuma zedoary and Kelp inhibited the tumor growth and the expression of metastasis-related proteins (MMPs, VEGF, pAkt, pERK1/2) and cystathionine beta synthase (CBS), one of endogenous Hydrogen sulfide (H2S) synthetase, in H22-bearing mice. Then it was observed that compatibility of curcumenol and laminarin inhibited proliferation, migration and invasion of human hepatoma HepG2 cells. Furthermore, we investigated the potential mechanism of compatibility of curcumenol and laminarin inhibiting HepG2 cell proliferation and metastasis. Our previous research showed that CBS/H2S system is vital for maintaining the proliferation of hepatoma cells. Here we found that the levels of pSTAT3 and BCL-2 were decreased in CBS kd HepG2 cells and the the compatibility of curcumenol and laminarin significantly decreased the H2S level at a dose-dependent manner and down-regulated the levels of pSTAT3 and BCL-2 in HepG2 cells. Angiogenesis positively regulated by vascular endothelial growth factor (VEGF) is essential for human cancer metastasis. In the present study, we found the compatibility of curcumenol and laminarin could significantly down-regulate the expression levels of VEGF and downstream key genes pAkt and pERK1/2. Furthermore, previous research showed that Hydrogen Sulfide can stimulate angiogenesis. Here we also observed the reduction of VEGF, Akt, pAkt, ERK1/2 and pERK1/2 proteins levels and the inhinition of proliferation and metastasis and in CBS kd HepG2 cells. Moreover, exogenous H2S rescued the cytological results caused by compatibility of curcumenol and laminarin. Taken together, the compatibility of curcuma zedoary and Kelp inhibited proliferation and metastasis of liver cancer in vivo and in vitro by the inhibition of endogenous H2S production and the down-regulation of pSTAT3/BCL-2 and VEGF pathway, which provides strong evidence for the application of curcuma zedoary and Kelp in treatments of liver cancer.

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Publication details

The article was received on 09 Aug 2018, accepted on 24 Nov 2018 and first published on 26 Nov 2018


Article type: Paper
DOI: 10.1039/C8FO01594E
Citation: Food Funct., 2018, Accepted Manuscript
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    Combination of curcuma zedoary and Kelp inhibits growth and metastasis of liver cancer in vivo and in vitro via reducing endogenous H2S level

    H. han, L. Wang, Y. Liu, X. shi, X. zhang, M. li and T. Wang, Food Funct., 2018, Accepted Manuscript , DOI: 10.1039/C8FO01594E

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