![Open Access](https://i-scholar.in/lib/pkp/templates/images/icons/fulltextgreen.png)
![Restricted Access](https://i-scholar.in/lib/pkp/templates/images/icons/fulltextred.png)
Chemopreventive Prospective of Dietary Spices against Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC), a primary liver cancer, is one of the most fatal cancers having universal prevalence. Developing countries of Asia and Africa are reported with more HCC cases compared to the United States and Europe. Surgical resection and liver transplantation present limited treatment choices for HCC. It is need of the hour to investigate promising alternative chemopreventive and therapeutic strategies to control the disease. In most cases HCC develops and progresses in an environment of inflammation and oxidative stress. Phytochemicals such as dietary spices and their active components gifted with potent anti-inflammatory and antioxidant properties, offer an appropriate alternative mitigation of HCC. Ginger, turmeric and garlic are the commonly used spices. Studies suggest that these have anti-inflammatory, antioxidant and antitumour activities. This article reviews their apoptotic, anti-inflammatory and antioxidant effects as well as involvement of various molecular signalling pathways.
Keywords
Apoptosis, Carcinogenesis, Chemoprevention, Hepatocellular Carcinoma, Inflammation.
User
Font Size
Information
- Darvesh, A. S., Aggarwal, B. B. and Bishayee, A., Curcumin and liver cancer: a review. Curr. Pharm. Biotechnol., 2012, 13, 218– 228.
- El-Serag, H. B. and Rudolph, K. L., Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology, 2007, 132, 2557–2576.
- Parkin, D. M., Bray, F., Ferlay, J. and Pisani, P., Global cancer statistics, 2002. CA Cancer J. Clin., 2005, 55, 74–108.
- Schutte, K., Bornschein, J. and Malfertheiner, P., Hepatocellular carcinoma – epidemiological trends and risk factors. Dig. Dis., 2009, 27, 80–92.
- Bartsch, H. and Montesano, R., Relevance of nitrosamines to human cancer. Carcinogenesis, 1984, 5, 1381–1393.
- Kensler, T. W. et al., Chemoprevention of hepatocellular carcinoma in aflatoxin endemic areas. Gastroenterology, 2004, 127, S310–S318.
- Ribes, J., Cleries, R., Esteban, L., Moreno, V. and Bosch, F. X., The influence of alcohol consumption and hepatitis B and C infections on the risk of liver cancer in Europe. J. Hepatol., 2008, 49, 233–242.
- Llovet, J. M., Burroughs, A. and Bruix, J., Hepatocellular carcinoma. Lancet, 2003, 362, 1907–1917.
- Mazzaferro, V. et al., Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N. Engl. J. Med., 1996, 334, 693–699.
- Singh, V. K. and Abrar, M., Medicinal Plants and Folklores, Today and Tomorrow Printers and Publishers, New Delhi, 1990.
- Sheeja, K., Shihab, P. K. and Kuttan, G., Antioxidant and antiinflammatory activities of the plant Andrographis paniculata Nees. Immunopharmacol. Immunotoxicol, 2006, 28, 129–140.
- Shoeb, M., Anticancer agents from medicinal plants. Bangladesh J. Pharmacol., 2006, 1, 35–41.
- Newman, D. J., Cragg, G. M. and Snader, K. M., Natural products as sources of new drugs over the period 1981–2002. J. Nat. Prod., 2003, 66, 1022–1037.
- Katiyar, S. K., Agarwal, R. and Mukhtar, H., Inhibition of tumor promotion in SENCAR mouse skin by ethanol extract of Zingiber officinale rhizome. Cancer Res., 1996, 56, 1023–1030.
- Manju, V. and Nalini, N., Chemopreventive efficacy of ginger, a naturally occurring anticarcinogen during the initiation, postinitiation stages of 1,2 dimethylhydrazine-induced colon cancer. Clin. Chim. Acta, 2005, 358, 60–67.
- Yusof, Y. A., Ahmad, N., Das, S., Sulaiman, S. and Murad, N. A., Chemopreventive efficacy of ginger (Zingiber officinale) in ethionine induced rat hepatocarcinogenesis. Afr. J. Tradit. Complement. Altern. Med., 2008, 6, 87–93.
- Habib, S. H., Makpol, S., Abdul Hamid, N. A., Das, S., Ngah, W. Z. and Yusof, Y. A., Ginger extract (Zingiber officinale) has anticancer and anti-inflammatory effects on ethionine-induced hepatoma rats. Clinics (Sao Paulo), 2008, 63, 807–813.
- Kundu, J. K. and Surh, Y. J., Breaking the relay in deregulated cellular signal transduction as a rationale for chemoprevention with anti-inflammatory phytochemicals. Mutat. Res., 2005, 591, 123–146.
- Arsura, M. and Cavin, L. G., Nuclear factor-kappaB and liver carcinogenesis. Cancer Lett., 2005, 229, 157–169.
- Aggarwal, B. B. and Shishodia, S., Molecular targets of dietary agents for prevention and therapy of cancer. Biochem. Pharmacol., 2006, 71, 1397–1421.
- Manju, V., Balasubramaniyan, V. and Nalini, N., Rat colonic lipid peroxidation and antioxidant status: the effects of dietary luteolin on 1,2-dimethylhydrazine challenge. Cell Mol. Biol. Lett., 2005, 10, 535–551.
- Cerutti, P. A., Oxy-radicals and cancer. Lancet, 1994, 344, 862– 863.
- Surh, Y., Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substances. Mutat. Res., 1999, 428, 305–327.
- Hu, H., Ahn, N. S., Yang, X., Lee, Y. S. and Kang, K. S., Ganoderma lucidum extract induces cell cycle arrest and apoptosis in MCF-7 human breast cancer cell. Int. J. Cancer, 2002, 102, 250– 253.
- Lee, E. and Surh, Y. J., Induction of apoptosis in HL-60 cells by pungent vanilloids, [6]-gingerol and [6]-paradol. Cancer Lett., 1998, 134, 163–168.
- Ammon, H. P. and Wahl, M. A., Pharmacology of Curcuma longa. Planta Med., 1991, 57, 1–7.
- Araujo, C. C. and Leon, L. L., Biological activities of Curcuma longa L. Mem. Inst. Oswaldo Cruz., 2001, 96, 723–728.
- Goel, A., Jhurani, S. and Aggarwal, B. B., Multi-targeted therapy by curcumin: how spicy is it? Mol. Nutr. Food Res., 2008, 52, 1010–1030.
- Goel, A., Kunnumakkara, A. B. and Aggarwal, B. B., Curcumin as ‘Curecumin’: from kitchen to clinic. Biochem. Pharmacol., 2008, 75, 787–809.
- Rivera-Espinoza, Y. and Muriel, P., Pharmacological actions of curcumin in liver diseases or damage. Liver Int., 2009, 29, 1457– 1466.
- Xiao, Y. et al., Furanodiene induces G2/M cell cycle arrest and apoptosis through MAPK signaling and mitochondria-caspase pathway in human hepatocellular carcinoma cells. Cancer Biol. Ther., 2007, 6, 1044–1050.
- Thornberry, N. A. and Lazebnik, Y., Caspases: enemies within. Science, 1998, 281, 1312–1316.
- Xiao, Y., Yang, F. Q., Li, S. P., Hu, G., Lee, S. M. and Wang, Y. T., Essential oil of Curcuma wenyujin induces apoptosis in human hepatoma cells. World J. Gastroenterol., 2008, 14, 4309–4318.
- Li, L., Aggarwal, B. B., Shishodia, S., Abbruzzese, J. and Kurzrock, R., Nuclear factor-kappaB and IkappaB kinase are constitutively active in human pancreatic cells, and their down-regulation by curcumin (diferuloylmethane) is associated with the suppression of proliferation and the induction of apoptosis. Cancer, 2004, 101, 2351–2362.
- Shakibaei, M., Schulze-Tanzil, G., John, T. and Mobasheri, A., Curcumin protects human chondrocytes from IL-l1 beta-induced inhibition of collagen type II and beta1-integrin expression and activation of caspase-3: an immunomorphological study. Ann. Anat., 2005, 187, 487–497.
- Handayani, T., Sakinah, S., Nallappan, M. and Pihie, A. H., Regulation of p53-, Bcl-2- and caspase-dependent signaling pathway in xanthorrhizol-induced apoptosis of HepG2 hepatoma cells. Anticancer Res., 2007, 27, 965–971.
- Cory, S., Huang, D. C. and Adams, J. M., The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene, 2003, 22, 8590–8607.
- Degli, E. M. and Dive, C., Mitochondrial membrane permeabilisation by Bax/Bak. Biochem. Biophys. Res. Commun., 2003, 304, 455–461.
- Hou, Q., Cymbalyuk, E., Hsu, S. C., Xu, M. and Hsu, Y. T., Apoptosis modulatory activities of transiently expressed Bcl-2: roles in cytochrome C release and Bax regulation. Apoptosis, 2003, 8, 617–629.
- Kluck, R. M., Bossy-Wetzel, E., Green, D. R. and Newmeyer, D. D., The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science, 1997, 275, 1132–1136.
- Yang, J. et al., Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science, 1997, 275, 1129– 1132.
- Oltvai, Z. N., Milliman, C. L. and Korsmeyer, S. J., Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell, 1993, 74, 609–619.
- Budihardjo, I., Oliver, H., Lutter, M., Luo, X. and Wang, X., Biochemical pathways of caspase activation during apoptosis. Annu. Rev. Cell Dev. Biol., 1999, 15, 269–290.
- Li, P. et al., Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell, 1997, 91, 479–489.
- Srinivasula, S. M., Ahmad, M., Fernandes-Alnemri, T. and Alnemri, E. S., Autoactivation of procaspase-9 by Apaf-1mediated oligomerization. Mol. Cell, 1998, 1, 949–957.
- Talanian, R. V. et al., Substrate specificities of caspase family proteases. J. Biol. Chem., 1997, 272, 9677–9682.
- Woo, M. et al., Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes. Genes Dev., 1998, 12, 806–819.
- Wang, W. H. et al., Curcumin-induced apoptosis in human hepatocellular carcinoma j5 cells: critical role of ca(+2)-dependent pathway. Evid. Based Complement. Altern. Med., 2012, 2012, 512907.
- Nakagawa, T. et al., Caspase-12 mediates endoplasmic-reticulumspecific apoptosis and cytotoxicity by amyloid-beta. Nature, 2000, 403, 98–103.
- Orrenius, S., Zhivotovsky, B. and Nicotera, P., Regulation of cell death: the calcium-apoptosis link. Nature Rev. Mol. Cell Biol., 2003, 4, 552–565.
- Ak, T. and Gulcin, I., Antioxidant and radical scavenging properties of curcumin. Chem. Biol. Interact., 2008, 174, 27–37.
- Osawa, T., Sugiyama, Y., Inayoshi, M. and Kawakishi, S., Antioxidative activity of tetrahydrocurcuminoids. Biosci. Biotechnol. Biochem., 1995, 59, 1609–1612.
- Sharma, O. P., Antioxidant activity of curcumin and related compounds. Biochem. Pharmacol., 1976, 25, 1811–1812.
- Sugiyama, Y., Kawakishi, S. and Osawa, T., Involvement of the beta-diketone moiety in the antioxidative mechanism of tetrahydrocurcumin. Biochem. Pharmacol., 1996, 52, 519–525.
- Milnerm, J. A., Mechanisms by which garlic and allyl sulfur compounds suppress carcinogen bioactivation. Garlic and carcinogenesis. Adv. Exp. Med. Biol., 2001, 492, 69–81.
- Siegel, G. et al., The effect of garlic on arteriosclerotic nanoplaque formation and size. Phytomedicine, 2004, 11, 24–35.
- Tsao, S. and Yin, M., In vitro activity of garlic oil and four diallyl sulphides against antibiotic-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae. J. Antimicrob. Chemother., 2001, 47, 665– 670.
- Colic, M. and Savic, M., Garlic extracts stimulate proliferation of rat lymphocytes in vitro by increasing IL-2 and IL-4 production. Immunopharmacol. Immunotoxicol., 2000, 22, 163–181.
- Salman, H., Bergman, M., Bessler, H., Punsky, I. and Djaldetti, M., Effect of a garlic derivative (alliin) on peripheral blood cell immune responses. Int. J. Immunopharmacol., 1999, 21, 589–597.
- Sundaram, S. G. and Milner, J. A., Impact of organosulfur compounds in garlic on canine mammary tumor cells in culture. Cancer Lett., 1993, 74, 85–90.
- Lorenson, M. Y., Cuccaro, M. L. and Jacobs, L. S., Calcium release from pituitary secretory granules: modulation by thiols, disulfides, and dihydropyridine calcium channel blockers. Endocrinology, 1990, 126, 2671–2678.
- Vamvakas, S., Bittner, D., Koob, M., Gluck, S. and Dekant, W., Glutathione depletion, lipid peroxidation, DNA double-strand breaks and the cytotoxicity of 2-bromo-3-(N-acetylcystein-S-yl) hydroquinone in rat renal cortical cells. Chem. Biol. Interact., 1992, 83, 183–199.
- Oshimi, Y. and Miyazaki, S., Fas antigen-mediated DNA fragmentation and apoptotic morphologic changes are regulated by elevated cytosolic Ca2+ level. J. Immunol., 1995, 154, 599–609.
- Morgan, D. O., Principles of CDK regulation. Nature, 1995, 374, 131–134.
- Pan, J., Hong, J. Y., Ma, B. L., Ning, S. M., Paranawithana, S. R. and Yang, C. S., Transcriptional activation of cytochrome P450 2B1/2 genes in rat liver by diallyl sulfide, a compound derived from garlic. Arch. Biochem. Biophys., 1993, 302, 337–342.
- Brady, J. F. et al., Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolites. Chem. Res. Toxicol., 1991, 4, 642–647.
- Wu, C. C., Sheen, L. Y., Chen, H. W., Kuo, W. W., Tsai, S. J. and Lii, C. K., Differential effects of garlic oil and its three major organosulfur components on the hepatic detoxification system in rats. J. Agric. Food Chem., 2002, 50, 378–383.
![](https://i-scholar.in/public/site/images/abstractview.png)
Abstract Views: 266
![](https://i-scholar.in/public/site/images/pdfview.png)
PDF Views: 95