Abstract
In this paper, the relationship of intracellular acidification and apoptosis in Hela cells induced by vincristine sulfate has been studied by use of the ratiometric pH nanosensors that have been developed by our group, employing fluorescein isothiocyanate (FITC) doped as the pH-sensitive dye and Tris(2,2′-bipyidyl) dichlororuthenium(II) hexahydrate (RuBpy) doped as reference dye. The pH change of the Hela cells induced by vincristine sulfate has been monitored in vivo, in situ and real time by use of the ratiometric pH nanosensors. The experimental results show that the pH of the apoptotic Hela cells induced by vincristine sulfate has been acidified from 7.11 to 6.51, and the percentage of intracellular acidification is correlated with the induced concentration and incubation time of the vincristine sulfate. The further study of the percentage of intracellular acidification and the percentage of apoptosis of Hela cells at the same time reveals that apoptosis of Hela cells induced by vincristine sulfate is preceded by intracellular acidification. These results would provide theoretical foundation for the therapy of cancer through interfering the pH of cells by use of vincristine sulfate or other anti-cancer drugs.
Similar content being viewed by others
References
Carson D A, Ribeiro J M. Apoptosis and disease. Lancet, 1993, 341: 1251–1254
McConkey D J, Orrenius S, Jondal M. Cellular signalling in programmed cell death (apoptosis). Immunol Today, 1990, 11(4): 120–121
Luo J D, Zheng P X, Chen X. Intracellular pH and apoptosis. Life Sci (in Chinese), 1997, 9(5): 218–221
Caceres-Cortes J, Rajotte D, Dumouchel J, et al. Product of the steel locus suppresses apoptosis in hemopoietic cells. Comparison with pathways activated by granulocyte macrophage colony-stimulating factor. J Biol Chem, 1994, 269(16): 12084–12091
Gottlieb R A, Giesing H, Zhu J Y, et al. Cell acidification in apoptosis: Granulocyte colony-stimulating factor delays programmed cell death in neutrophils by up-regrading the vacuolar H+-ATPase. P Natl Acad Sci USA, 1995, 92: 5965–5968
Gottlieb R A, Nordberg J, Skowronski E, et al. Apoptosis induced in Jurkat cells by several agents in preceded by intracellular acidification. P Natl Acad Sci USA, 1996, 93: 654–658
Ji J, Rosenzweig N, Griffin C, et al. Synthesis and application of submicrometer fluorescence sensing particles for lysosomal pH measurements in murine macrophages. Anal Chem, 2000, 72: 3497–3503
Song A, Parus S, Kopelman R. High-performance fiber-optic pH microsensors for practical physiological measurements using a dualemission sensitive dye. Anal Chem, 1997, 69: 863–867
Bui J D, Zelles T, Lou H J, et al. Probing intracellular dynamics in living cells with near-field optics. J Neurosci Meth, 1999, 89: 9–13
Clark H A, Hoyer M, Philbert M A, et al. Optical nanosensors for chemical analysis inside single living cells. 1. Fabrication, characterization, and methods for intracellular delivery of PEBBLE sensors. Anal Chem, 1999, 71: 4831–4836
Clark H A, Kopelman R, Tjalkens R, et al. Optical nanosensors for chemical analysis inside single living cells. 2. Sensors for pH and calcium and the intracellular application of PEBBLE sensors. Anal Chem, 1999, 71: 4837–4843
McNamara K P, Nguyen T, Dumitrascu G, et al. Synthesis, characterization, and application of fluorescence sensing lipobeads for intracellular pH measurements. Anal Chem, 2001, 73: 3240–3246
Wang K M, Tan W H, Peng J F, et al. Preparation of ratiometric pH nanosensors and application in noninvasive monitoring of intracellular pH change (in Chinese). China Patent, 2004100467941, 2004-09-24
Clark H A, Barker S L R, Brasuel M, et al. Subcellular optochemical nanobiosensors: Probes encapsulated by biologically localised embedding (PEBBLEs). Sensor Actuat B-Chem, 1998, 51: 12–16
Park E J, Brasuel M, Behrend C, et al. Ratiometric optical PEBBLE nanosensors for real-time magnesium ion concentrations inside viable cells. Anal Chem, 2003, 75: 3784–3791
Xing X L, He X X, Peng J F, et al. Investigation of uptake of silica-coated nanoparticles by Hela cells. J Nanosci & Nanotech, 2005, 5: 1–6
Li W L, Huang G J. Antitumor strategy targeting on pH regulation mechanism of cancer cells. Overseas Med Oncol Fasc (in Chinese), 1997, 24(2): 73–74
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by the Key Project of National Natural Science Foundation of China (Grant No. 20135010), the National Key Basic Research Program of China (Grant No. 2002CB513100-10), the Key Technology Research and Development Program of China (Grant No. 2003BA310A16), the High-Tech Research and Development Program of China (Grant No. 2003AA302250), the International Cooperation Key Project of Science and Technology Ministry (Grant No. 2003DF000039) and the National Natural Science Foundation of China (Grant No. 20405005)
Rights and permissions
About this article
Cite this article
He, X., Wang, Y., Wang, K. et al. Research of the relationship of intracellular acidification and apoptosis in Hela cells based on pH nanosensors. SCI CHINA SER B 50, 258–265 (2007). https://doi.org/10.1007/s11426-007-0012-1
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11426-007-0012-1