Diallyl trisulfide induces apoptosis in human primary colorectal cancer cells

Yu,Chun-Shu; Huang,An-Cheng; Lai,Kuang-Chi; Huang,Yi-Ping; Lin,Meng-Wei; Yang,Jai-Sing; Chung,Jing-Gung

doi:10.3892/or.2012.1882

Diallyl trisulfide induces apoptosis in human primary colorectal cancer cells

Authors:
- Chun-Shu Yu
- An-Cheng Huang
- Kuang-Chi Lai
- Yi-Ping Huang
- Meng-Wei Lin
- Jai-Sing Yang
- Jing-Gung Chung
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Affiliations: School of Pharmacy, China Medical University, Taichung 404, Taiwan, R.O.C., Department of Nursing, St. Mary's Medicine Nursing and Management College, Yilan 266, Taiwan, R.O.C., School of Medicine, China Medical University, Taichung 404, Taiwan, R.O.C., Department of Physiology, China Medical University, Taichung 404, Taiwan, R.O.C., Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan, R.O.C., Department of Pharmacology, China Medical University, Taichung 404, Taiwan, R.O.C.
Published online on: June 20, 2012 https://doi.org/10.3892/or.2012.1882
Pages: 949-954

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Abstract

Colorectal cancer (CRC) is one of the most prevalent types of cancer worldwide and a common cause of morbidity and mortality in humans. The garlic-derived organosulfur compound diallyl trisulfide (DATS) has been shown to induce apoptosis in many human cancer cell lines in vitro and also affords significant protection against cancer in animal tumor models in vivo. There is no available information to show DATS-induced apoptosis in vitro and the molecular mechanisms of apoptosis in human primary colorectal cancer cells. In this study, we investigated the cytotoxic effects in DATS in primary colorectal cancer cells. DATS inhibited the viability of primary colorectal cancer cells in a time- and dose-dependent manner. After treatment with DATS, primary colorectal cancer cells exhibited DNA condensation by DAPI stain. DATS increased reactive oxygen species (ROS) production in primary colorectal cancer cells. The mitochondria-dependent apoptotic signaling pathway was shown to be involved as determined by increase in the levels of cytochrome c, Apaf-1, AIF and caspase-3 and caspase-9 in DATS-treated primary colorectal cancer cells. The decrease in the level of ΔΨm was associated with an increase in the Bax/Bcl-2 ratio which led to activation of caspase-9 and -3. Based on our results, DATS induces apoptotic cell death in human primary colorectal cancer cells through a mitochondria-dependent signaling pathway.

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1	Jaramillo S, Lopez S, Varela LM, et al: The flavonol isorhamnetin exhibits cytotoxic effects on human colon cancer cells. J Agric Food Chem. Oct 5–2010.(Epub ahead of print).
2	Nautiyal J, Banerjee S, Kanwar SS, et al: Curcumin enhances dasatinib-induced inhibition of growth and transformation of colon cancer cells. Int J Cancer. 128:951–961. 2011. View Article : Google Scholar : PubMed/NCBI
3	van Duijnhoven FJ, Bueno-De-Mesquita HB, Ferrari P, et al: Fruit, vegetables, and colorectal cancer risk: the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr. 89:1441–1452. 2009.
4	Davis CD and Milner JA: Gastrointestinal microflora, food components and colon cancer prevention. J Nutr Biochem. 20:743–752. 2009. View Article : Google Scholar : PubMed/NCBI
5	Fadeel B and Orrenius S: Apoptosis: a basic biological phenomenon with wide-ranging implications in human disease. J Intern Med. 258:479–517. 2005. View Article : Google Scholar : PubMed/NCBI
6	Adams JM and Cory S: Bcl-2-regulated apoptosis: mechanism and therapeutic potential. Curr Opin Immunol. 19:488–496. 2007. View Article : Google Scholar : PubMed/NCBI
7	Maiuri MC, Zalckvar E, Kimchi A and Kroemer G: Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 8:741–752. 2007. View Article : Google Scholar : PubMed/NCBI
8	Huttemann M, Pecina P, Rainbolt M, et al: The multiple functions of cytochrome c and their regulation in life and death decisions of the mammalian cell: from respiration to apoptosis. Mitochondrion. 11:369–381. 2011. View Article : Google Scholar : PubMed/NCBI
9	Kao ST, Yeh CC, Hsieh CC, et al: The Chinese medicine Bu-Zhong-Yi-Qi-Tang inhibited proliferation of hepatoma cell lines by inducing apoptosis via G0/G1 arrest. Life Sci. 69:1485–1496. 2001. View Article : Google Scholar : PubMed/NCBI
10	Martinou JC and Youle RJ: Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev Cell. 21:92–101. 2011. View Article : Google Scholar : PubMed/NCBI
11	Antony ML and Singh SV: Molecular mechanisms and targets of cancer chemoprevention by garlic-derived bioactive compound diallyl trisulfide. Indian J Exp Biol. 49:805–816. 2011.PubMed/NCBI
12	Seki T, Hosono T, Hosono-Fukao T, et al: Anticancer effects of diallyl trisulfide derived from garlic. Asia Pac J Clin Nutr. 17(Suppl 1): 249–252. 2008.PubMed/NCBI
13	Li N, Guo R, Li W, et al: A proteomic investigation into a human gastric cancer cell line BGC823 treated with diallyl trisulfide. Carcinogenesis. 27:1222–1231. 2006. View Article : Google Scholar : PubMed/NCBI
14	Sakamoto K, Lawson LD and Milner JA: Allyl sulfides from garlic suppress the in vitro proliferation of human A549 lung tumor cells. Nutr Cancer. 29:152–156. 1997. View Article : Google Scholar : PubMed/NCBI
15	Hosono T, Fukao T, Ogihara J, et al: Diallyl trisulfide suppresses the proliferation and induces apoptosis of human colon cancer cells through oxidative modification of beta-tubulin. J Biol Chem. 280:41487–41493. 2005. View Article : Google Scholar : PubMed/NCBI
16	Pinto JT and Rivlin RS: Antiproliferative effects of allium derivatives from garlic. J Nutr. 131:S1058–S1060. 2001.PubMed/NCBI
17	Chun HS, Kim HJ and Choi EH: Modulation of cytochrome P4501-mediated bioactivation of benzo[a]pyrene by volatile allyl sulfides in human hepatoma cells. Biosci Biotechnol Biochem. 65:2205–2212. 2001.PubMed/NCBI
18	Antosiewicz J, Herman-Antosiewicz A, Marynowski SW and Singh SV: c-Jun NH(2)-terminal kinase signaling axis regulates diallyl trisulfide-induced generation of reactive oxygen species and cell cycle arrest in human prostate cancer cells. Cancer Res. 66:5379–5386. 2006. View Article : Google Scholar
19	Xiao D, Zeng Y, Hahm ER, Kim YA, Ramalingam S and Singh SV: Diallyl trisulfide selectively causes Bax- and Bak-mediated apoptosis in human lung cancer cells. Environ Mol Mutagen. 50:201–212. 2009. View Article : Google Scholar : PubMed/NCBI
20	Xiao D, Choi S, Johnson DE, et al: Diallyl trisulfide-induced apoptosis in human prostate cancer cells involves c-Jun N-terminal kinase and extracellular-signal regulated kinase-mediated phosphorylation of Bcl-2. Oncogene. 23:5594–5606. 2004. View Article : Google Scholar
21	Ji C, Ren F and Xu M: Caspase-8 and p38MAPK in DATS-induced apoptosis of human CNE2 cells. Braz J Med Biol Res. 43:821–827. 2010. View Article : Google Scholar : PubMed/NCBI
22	Lai KC, Hsu SC, Kuo CL, et al: Diallyl sulfide, diallyl disulfide, and diallyl trisulfide inhibit migration and invasion in human colon cancer colo 205 cells through the inhibition of matrix metalloproteinase-2, -7, and -9 expressions. Environ Toxicol. Jun 21–2011.(Epub ahead of print).
23	Wu PP, Liu KC, Huang WW, et al: Diallyl trisulfide (DATS) inhibits mouse colon tumor in mouse CT-26 cells allograft model in vivo. Phytomedicine. 18:672–676. 2011. View Article : Google Scholar : PubMed/NCBI
24	Lai KC, Chiu YJ, Tang YJ, et al: Houttuynia cordata Thunb extract inhibits cell growth and induces apoptosis in human primary colorectal cancer cells. Anticancer Res. 30:3549–3556. 2010.PubMed/NCBI
25	Lu CC, Yang JS, Huang AC, et al: Chrysophanol induces necrosis through the production of ROS and alteration of ATP levels in J5 human liver cancer cells. Mol Nutr Food Res. 54:967–976. 2010. View Article : Google Scholar : PubMed/NCBI
26	Chiang JH, Yang JS, Ma CY, et al: Danthron, an anthraquinone derivative, induces DNA damage and caspase cascades-mediated apoptosis in SNU-1 human gastric cancer cells through mitochondrial permeability transition pores and Bax-triggered pathways. Chem Res Toxicol. 24:20–29. 2011. View Article : Google Scholar
27	Ho YT, Lu CC, Yang JS, et al: Berberine induced apoptosis via promoting the expression of caspase-8, -9 and -3, apoptosis-inducing factor and endonuclease G in SCC-4 human tongue squamous carcinoma cancer cells. Anticancer Res. 29:4063–4070. 2009.
28	Yang JS, Hour MJ, Huang WW, Lin KL, Kuo SC and Chung JG: MJ-29 inhibits tubulin polymerization, induces mitotic arrest, and triggers apoptosis via cyclin-dependent kinase 1-mediated Bcl-2 phosphorylation in human leukemia U937 cells. J Pharmacol Exp Ther. 334:477–488. 2010. View Article : Google Scholar
29	Ying WZ and Sanders PW: Cytochrome c mediates apoptosis in hypertensive nephrosclerosis in Dahl/Rapp rats. Kidney Int. 59:662–672. 2001. View Article : Google Scholar : PubMed/NCBI
30	Chandra-Kuntal K and Singh SV: Diallyl trisulfide inhibits activation of signal transducer and activator of transcription 3 in prostate cancer cells in culture and in vivo. Cancer Prev Res (Phila). 3:1473–1483. 2010. View Article : Google Scholar : PubMed/NCBI
31	Iciek M, Kwiecien I, Chwatko G, Sokolowska-Jezewicz M, Kowalczyk-Pachel D and Rokita H: The effects of garlic-derived sulfur compounds on cell proliferation, caspase 3 activity, thiol levels and anaerobic sulfur metabolism in human hepatoblastoma HepG2 cells. Cell Biochem Funct. 30:198–204. 2011. View Article : Google Scholar
32	Lee BC, Park BH, Kim SY and Lee YJ: Role of Bim in diallyl trisulfide-induced cytotoxicity in human cancer cells. J Cell Biochem. 112:118–127. 2011. View Article : Google Scholar : PubMed/NCBI
33	Xiao D and Singh SV: Diallyl trisulfide, a constituent of processed garlic, inactivates Akt to trigger mitochondrial translocation of BAD and caspase-mediated apoptosis in human prostate cancer cells. Carcinogenesis. 27:533–540. 2006. View Article : Google Scholar