S-benzyl-cysteine-mediated Cell Cycle Arrest and Apoptosis Involving Activation of Mitochondrial-dependent Caspase Cascade through the p53 Pathway in Human Gastric Cancer SGC-7901 Cells

  • Sun, Hua-Jun (Department of Pharmacy, Shanghai Children's Hospital, Shanghai Jiaotong University) ;
  • Meng, Lin-Yi (Department of Pharmacy, Shanghai Children's Hospital, Shanghai Jiaotong University) ;
  • Shen, Yang (Department of Pharmacy, Shanghai Children's Hospital, Shanghai Jiaotong University) ;
  • Zhu, Yi-Zhun (Department of Pharmacology, School of Pharmacy, Fudan University) ;
  • Liu, Hong-Rui (Department of Pharmacology, School of Pharmacy, Fudan University)
  • Published : 2013.11.30


S-benzyl-cysteine (SBC) is a structural analog of S-allylcysteine (SAC), which is one of the major water-soluble compounds in aged garlic extract. In this study, anticancer activities and the underlying mechanisms of SBC action were investigated and compared these with those of SAC using human gastric cancer SGC-7901 cells. SBC significantly suppressed the survival rate of SGC-7901 cells in a concentration- and time-dependent manner, and the inhibitory activities of SBC were stronger than those of SAC. Flow cytometry revealed that SBC induced G2-phase arrest and apoptosis in SGC-7901 cells. Typical apoptotic morphological changes were observed by Hoechst 33258 dye assay. SBC-treatment dramatically induced the dissipation of mitochondrial membrane potential (${\Delta}{\Psi}m$), and enhanced the enzymatic activities of caspase-9 and caspase-3 whilst hardly affecting caspase-8 activity. Furthermore, Western blotting indicated that SBC-induced apoptosis was accompanied by up-regulation of the expression of p53, Bax and the down-regulation of Bcl-2. Taken together, this study suggested that SBC exerts cytotoxic activity involving activation of mitochondrial-dependent apoptosis through p53 and Bax/Bcl-2 pathways in human gastric cancer SGC-7901 cells.


Aged garlic extract;apoptosis-cell cycle;SGC-7901 cell;p53 signalling pathway


  1. Chao JI, Kuo PC, Hsu TS (2004). Down-regulation of survivin in nitric oxide induced cell growth inhibition and apoptosis of the human lung carcinoma cells. J Biol Chem, 279, 20267-6.
  2. Chipuk JE, Green DR (2008). How do Bcl-2 proteins induce mitochondrial outer membrane permeabilization? Trends Cell Biol, 18, 157-64.
  3. Chu Q, Ling MT, Feng H, et al (2006). A novel anticancer effect of garlic derivatives: inhibition of cancer cell invasion through restoration of E-cadherin expression. Carcinogenesis, 27, 2180-9.
  4. Cryns V, Yuan J (1998). Proteases to die for. Genes Dev, 12, 1551-70.
  5. Danaei G, Vander Hoorn S, Lopez AD, et al (2005). Causes of cancer in the world: comparative risk assessment of nine behavioural and environmental risk factors. Lancet, 366, 1784-93.
  6. Davis SR (2005). An overview of the antifungal properties of allicin and its breakdown products-the possibility of a safe and effective antifungal prophylactic. Mycoses, 48, 95-100.
  7. Fujita K, Kimura M, Kondo N, et al (1992). Anti-tumor effects of telomelysin for head and neck squamous cell carcinoma. Oncol Rep, 20, 1363-8.
  8. Harris SL, Levine AJ (2005). The p53 pathway: positive and negative feedback loops. Oncogene, 24, 2899-908.
  9. Heimlich G, McKinnon AD, Bernardo K, et al (2004). Bax-induced cytochrome c release from mitochondria depend sonalphahelices-5 and-6. Biochem J, 378, 247-55.
  10. Hoffman WH, Biade S, Zilfou JT, Chen J, Murphy M (2002).Transcriptional repression of the anti-apoptotic survivin gene by wild type p53. J Biol Chem, 277, 3247-57.
  11. Hofseth LJ, Hussain SP, Harris CC (2004). p53: 25 years after its discovery. Trends Pharmacol Sci, 25, 177-81.
  12. Hong YS, Ham YA, Choi JH, et al (2000). Effects of allyl sulfur compounds and garlic extract on the expressions of Bcl-2, Bax, and p53 in non small cell lung cancer cell lines. Exp Mol Med, 32, 127-34.
  13. Imai J, Ide N, Nagae S, et al (1994). Antioxidant and radical scavenging effects of aged garlic extract and its constituents. Planta Med, 60, 417-20.
  14. Kundu T, Dey S, Roy M, et al (2005). Induction of apoptosis in human leukemia cells by black tea and its polyphenol theaflavin. Cancer Lett, 230, 111-21.
  15. Lane DP (1992). p53, guardian of the genome. Nature, 358, 15-6.
  16. Liu HR, Meng LY, Lin ZY, et al (2012). Cochinchina momordica seed extract induces apoptosis and cell cycle arrest in human gastric cancer cells via PARP and p53 signal pathways. Nutr Cancer, 64, 1070-7
  17. Mukherjee S, Banerjee SK, Maulik M, et al (2003). Protection against acute Adriamycin induced cardiotoxicity by garlic: role of endogenous antioxidants and inhibition of TNF-alpha expression. BMC Pharmacol, 3, 16.
  18. Nagini S (2008). Cancer chemoprevention by garlic and its organosulfur compounds: panacea or promise? Anticancer Agents Med Chem, 8, 313-21.
  19. Penninger JM, Kroemer G (1996). Molecular and cellular mechanisms of T lymphocyte apoptosis. Adv Immunol, 68, 51-144.
  20. Pu L, Amoscato AA, Bier ME, Lazo JS (2002). Dual G1 and G2 phase inhibition by a novel, selective Cdc25 inhibitor 6-chloro-7-[corrected](2-morpholin-4-ylethylamino)-quinoline-5, 8-dione. J Biol Chem, 277, 46877-85.
  21. Rose P, Whiteman M, Moore PK, et al (2005). Bioactive S-alk(en)yl cysteine sulfoxide metabolites in the genus Allium: the chemistry of potential therapeutic agents. Nat Prod Rep, 22, 351-68.
  22. Sandhu SK, Yap TA, de Bono JS (2010). Poly (ADP-ribose) polymerase inhibitors in cancer treatment: a clinical perspective. Eur J Cancer, 46, 9-20.
  23. Schluep T, Gunawan P, Ma L, et al (2009). Polymeric tubulysin-peptide nanoparticles with potent antitumor activity. Clin Cancer Res, 15, 181-9.
  24. Shen J, Davis LE, Wallace JM, et al (1996). Enhanced diallyl trisulfide has in vitro synergy with amphotericin B against Cryptococcus neoformans. Planta Med, 62, 415-8.
  25. Smith ML, Kumar MA (2010). The "two faces" of tumor suppressor p53-revisited. Mol Cell Pharmacol, 2, 117-9.
  26. Sun WG, Wei-Li Xu, Hui-Kun Liu (2009). gamma-Tocotrienol induces mitochondria-mediated apoptosis in human gastric adenocarcinoma SGC-7901 cells. J Nutr Biochem, 20, 276-84.
  27. Wang Q, Liu HR, Mu Q, et al (2009). S-propargyl-cysteine protects both adult rat hearts and neonatal cardiomyocytes from ischemia/hypoxia injury: the contribution of the hydrogen sulfide-mediated pathway. J Cardiovasc Pharmacol, 54, 139-46.
  28. Wang Y, Ji P, Liu J, et al (2009). Centrosome-associated regulators of the G(2)/M checkpoint as targets for cancer therapy. Mol Cancer, 8, 8.
  29. Yamaguchi H, Bhalla K, Wang HG (2003). Bax plays a pivotal role in thapsigargin-induced apoptosis of human colon cancer HCT116 cells by controlling Smac/Diablo and Omi/HtrA2 release from mitochondria. Cancer Res, 63, 1483-9.
  30. Yip KW, Reed JC (2008). Bcl-2 family proteins and cancer. Oncogene, 27, 6398-406
  31. Zhang ZM, Yang XY, Deng SH, et al (2007). Anti-tumor effects of polybutylcyanoacrylate nanoparticles of diallyl trisulfide on orthotopic transplantation tumor model of hepatocellular carcinoma in BALB/c nude mice. Chin Med J, 120, 1336-42.

Cited by

  1. Fenofibrate Increases Radiosensitivity in Head and Neck Squamous Cell Carcinoma via Inducing G2/M Arrest and Apoptosis vol.15, pp.16, 2014,
  2. Phase Arrest and Apoptosis in Human Hepatoma SMMC-7721 Cells vol.15, pp.3, 2014,
  3. Rice Bran Phytic Acid Induced Apoptosis Through Regulation of Bcl-2/Bax and p53 Genes in HepG2 Human Hepatocellular Carcinoma Cells vol.15, pp.8, 2014,
  4. Knockdown of Glutamate Cysteine Ligase Catalytic Subunit by siRNA Causes the Gold Nanoparticles-Induced Cytotoxicity in Lung Cancer Cells vol.10, pp.3, 2015,
  5. Therapeutic Role of Functional Components in Alliums for Preventive Chronic Disease in Human Being vol.2017, pp.1741-4288, 2017,