Prohibitin Induces Apoptosis in BGC823 Gastric Cancer Cells Through the Mitochondrial Pathway

  • Zhang, Long (Interventional Oncology Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine) ;
  • Ji, Qing (Interventional Oncology Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine) ;
  • Ni, Zhen-Hua (Interventional Oncology Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine) ;
  • Sun, Jian (Interventional Oncology Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine)
  • Published : 2012.08.31


Prohibitin (PHB), an evolutionarily-conserved protein, has been found to be over-expressed in gastric cancer and be closely related with tumor malignancy. In this study, to investigate the relationship between PHB expression and cell apoptosis in the BGC823 gastric cancer cell line, low and high expression PHB in BGC823 cells was accomplished using RNA interference technology and gene transfer techniques. Cell proliferation, cell cycling, apoptosis, Bax, Bcl-2 and Cyt.c protein expression and the activation of Caspase-3,9 were assessed after 48h. Over-expression of PHB gene in BGC823 cells resulted in slow cell growth, cell arrest in G2 phase, and an increased apoptosis ratio while the opposite was found for PHB under-expressing cells. In PHB over-expressing cells, the expression of Bax gene was increased, the expression of Bcl-2 was decreased, the activation level of Caspase-3, 9 was increased, but the activation level of Caspase-8 demonstrated no change. These results indicate that PHB induced apoptosis through the mitochondrial pathway.


Prohibitin;apoptosis;BGC823;mitochondrial pathway


  1. Alenzi FQ, Lotfy M, Wyse R (2010). Swords of cell death: caspase activation and regulation. Asian Pac J Cancer Prev, 11, 271-80
  2. Artal-Sanz M, Tsang WY, Willems, et al (2003).The mitochondrial prohibitin complex is essential for embryonic viability and germline function in Caenorhabditis elegans. J Biol Chem, 27, 32091-99.
  3. Berger KH, MP Yaffe (1998). Prohibitin family members interact genetically with mitochondrial inheritance components in Saccharomyces cerevisiae. Molec Cellular Biol, 18, 4043-52.
  4. Coates PJ, Jamieson DJ, Smart K, et al (1997). The prohibitin family of mitochondrial proteins regulate replicative lifespan. Current Biology, 7607-10.
  5. Fang Min, Wang Xiaodong (2002). Mitochondrial apoptosis pathway. J Peking University (Health Sciences), 34, 1-7.
  6. Ikonen E, Fiedler K, Parton RG, et al (1995). Prohibitin, an antiproliferative protein, is localized to mitochondria. FEBS Letters, 35, 8273-7.
  7. Ji Qi, Zhang Long, Sun Jian, et al (2010). Investigation on expression level of PHBI in gastric and colorectal cancer by real time PCR. Lab Med Clin, 7332-3.
  8. Jorg M, Angela P, Peter S, et al (2004). Differential immunization identifies PHB1/PHB2 as blood-borne tumor antigens. Oncogene, 23, 7430-5.
  9. Jupe ER, Liu XT, Kiehlbauch JL, et al (1996). The 3' untranslated region of prohibitin and cellular immortalization. Exp Cell Res, 22, 4128-35.
  10. Kang X, Zhang L, Sun J, et al (2008). Prohibitin: a potential biomarker for tissue-based detection of gastric cancer. J Gastroenterol, 43, 618-25.
  11. Kang X, Zhang L, Wu R, et al (2006). The expression of Prohibitin in gastrointestinal cancer tissue and its clinical significance. Lab Med, 21, 610-2.
  12. Korsmeyer SJ, Wei MC, Saito M, et al (2000). Pro-apoptotic cascade activates BID ,which oligomerizes BAKor BAX into pores that result in the release of cytochrome-c. Cell Death Differ, 71, 166- 73.
  13. Leo GJ, Liesbeth DJ, Marta AS, et al (2000). Prohibitins act as a membrane-bound chaperone for the stabilization of mitochondrial proteins. EMBO J, 19, 2444-51
  14. Nora M, Alicia G, Mariel N, et al (2005). Mitochondrial apoptotic pathways. Biocell, 29, 149-61
  15. Ren H, Du N, Liu G, et al (2006). Analysis of variabilities of serum proteomic spectra in patients with gastric cancer before and after operation. World J Gastroenterol, 12, 2789-92.
  16. Shi CL, Yu CH, Zhang Y, et al (2011). Monocyte chemoattractant protein-1 modulates invasion and apoptosis of PC-3M prostate cancer cells via regulating expression of VEGF, MMP9 and caspase-3. Asian Pac J Cancer Prev, 12, 555-9
  17. Snedden WA, Fromm H (1997). Characterization of the plant homologue of prohibitin, a gene associated with antiproliferative activity in mammalian cells. Plant Molecular Biology, 33, 753-6.
  18. Spurdle AB, Hopper JL, Chen XQ, et al (2002). Prohibitin 3' untranslated region polymorphism and breast cancer risk in Australian women. Lancet, 360, 925-26.
  19. Sun ZL, Zhu Y, Wang FQ (2007). Serum proteomic-based analysis of pancreatic carcinoma for the identification of potential cancer biomarkers. Biochimica et Biophysica Acta, 1774, 764-71.
  20. Wolf B, Sehuler M, Eeheverrl F, et a1 (1999). Caspase-3 is the primary activator of apoptotic DNA fragmentation via DNA fragment factor45/inhibitor of caspase activated DNase activation. Biol Chem, 274, 30651-6.
  21. Zhang L, Ni Z, Wu R, et al (2009). Expression of Prohibitin and application of recombinant Prohibitin in serologic diagnosis. Contemporary Med, 77, 1-4.

Cited by

  1. Effect of lentinan combined with docetaxel and cisplatin on the proliferation and apoptosis of BGC823 cells vol.34, pp.3, 2013,
  2. Tetrandrine Induces Mitochondria-Mediated Apoptosis in Human Gastric Cancer BGC-823 Cells vol.8, pp.10, 2013,
  3. Over-Expressing Prohibitin (PHB) in Neuronal Cultures Exacerbates Cell Death Following Hydrogen Peroxide and L-Glutamic Acid Induced Injury vol.05, pp.04, 2014,
  4. Multifaceted role of prohibitin in cell survival and apoptosis vol.20, pp.9, 2015,
  5. Identification of prohibitin 1 as a potential prognostic biomarker in human pancreatic carcinoma using modified aqueous two-phase partition system combined with 2D-MALDI-TOF-TOF-MS/MS vol.36, pp.2, 2015,
  6. Differences in Beef Quality between Angus (Bos taurus taurus) and Nellore (Bos taurus indicus) Cattle through a Proteomic and Phosphoproteomic Approach vol.12, pp.1, 2017,
  7. Japanese encephalitis virus induces human neural stem/progenitor cell death by elevating GRP78, PHB and hnRNPC through ER stress vol.8, pp.1, 2017,
  8. Lentinan inhibits tumor angiogenesis via interferon γ and in a T cell independent manner vol.37, pp.1, 2018,
  9. A novel prognostic marker and immunogenic membrane antigen: prohibitin (PHB) in pancreatic cancer vol.9, pp.9, 2018,
  10. Significance of prohibitin domain family in tumorigenesis and its implication in cancer diagnosis and treatment vol.9, pp.6, 2018,