Abstract
Heat treatment of Panax ginseng C.A. Meyer at a temperature higher than that applied to the conventional preparation of Korea ginseng has been reported to yield a mixture of saponins with potent cytotoxic properties. In an effort to understand the mechanism of cytotoxicity, we studied the effect of heat-processed crude saponin (H-CS) on the viability, nuclear morphology and apoptotic gene induction of human colorectal carcinoma cells (HCT-15 cells) and human glioma carcinoma cells (U87MG). Treatment of the carcinoma cells with a final concentration of up to 1 mg/mL of H-CS resulted in a dose-dependent decrease in viability. In comparison with non-heatprocessed crude saponin (NH-CS), H-CS exhibited increased cytotoxicity. In addition, H-CS induced more apoptotic nuclear fragments in HCT-15 cells than in NH-CS. An analysis of apoptotic gene expression using quantitative real-time PCR revealed high expression levels of the genes encoding caspase 7, caspase 9, cytochrome C, and Bax at RQ values of 26.87, 17.39, 4.55, and 8.51, respectively. Collectively, our results suggest that H-CS has higher anti-proliferative effects on carcinoma cells by inducing apoptosis of the mitochondrial pathway.
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References
Baek, N. I. et al. Ginsenoside Rh4: a genuine damarane glycoside from Korean red ginseng. Planta Med 62: 86–87 (1996).
Kubo, M., Tong, C. N. & Matsuda, H. Influence of 70% methanolic extract from red ginseng on the lysosome of tumor cells and on the cytocidal effect of mitomycin C. Planta Med 58:424–428 (1992).
Chang, Y. S. et al. Panax ginseng: A role in cancer therapy? Inter Cancer Ther 2:13–33 (2003).
Wakayabashi, C. et al. An intestinal bacterial metabolite of ginseng protopanaxadiol saponins has the ability to induce apoptosis in tumor cells. Biochem Biophys Res Commun 246:725–730 (1998).
Nagai, M. et al. Chemical studies on the oriental plant drugs. XXVIII. Saponins and sapogenins of ginseng: stereochemistry of the sapogenin of ginsenoside Rb1, Rb2 and Rc. Chem Pharm Bull 20:1212–1216 (1972).
Park, J. A. et al. Activation of caspase-3 protease via a Bcl-2-insensitive pathway during the process of ginsenoside Rh2-induced apoptosis. Cancer Lett 121:73–81 (1997).
Park, J. H. et al. A new processed ginseng with fortified activity, in: Hug H, Choi KJ, Kim YC (Eds), Advances in Ginseng Research (Proceedings of the 7th international Symposium on Ginseng), Korean Society of Ginseng Seoul, South Korea, 146–159 (1998).
Zhu, J. H. et al. Suppression of the formation of sister chromatid exchanges by low concentrations of ginsenoside Rh2 in human blood lymphocytes. Cancer Res 55:1221–1223 (1995).
Mochizuki, M. et al. Inhibitory effect of tumor metastasis in mice by saponins, ginsenoside-Rb2, 20(R)- and 20(S)-ginsenoside-Rg3, of red ginseng. Biol Pharm Bull 18:1197–1202 (1995).
Fishbein, A. B. et al. Asian ginseng enhances the antiproliferative effect of 5-fluorouracil on human colorectal cancer: Comparison between white and red ginseng. Arch Pharm Res 32:505–513 (2009).
Kim, J. Y. et al. Isoliquiritigenin isolated from the roots of Glycyrrhiza uralensis inhibits LPS-induced iNOS and COX.2 expression via the attenuation of NF-kappaB in RAW264.7macrophages. Eur J Pharmacol 584:175–184 (2009).
Kun, W. et al. R-α-tocopheryl succinate inhibits human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesis arrest? World J Gastroenterol 8:26–30 (2002).
Yun, T. K. Panax ginseng- a non-organ-specific cancer preventive? Lancet Oncol 2:49–54 (2001).
Surh, Y. J., et al. Molecular mechanisms underlying anti-tumor promoting activities of heat-processed panax ginseng C.A. Meyer. J Korean Med Sci 16:38–41 (2001).
Laurent, M., Sonia, M. C. & Kathleen, W. K. Is MAC the knife that cuts cytochrome c from mitochondria during apoptosis? Cell Death Differ 13: 1385–1387 (2006).
Kluck, R. M. et al. The release of cytochrome c from mitochondira: a primary site for Bcl-2 regulation of apoptosis. Science 275:1132–1136 (1997).
Brzuzan, P. et al. Real-time PCR analysis of p53 mRNA levels in tissues of whitefish (Coregonus lavaretus) exposed to benxo[α]pyrene. Pol J Betenin Sci 9:139–145 (2006).
Kanli, A. & Sacli, H. Differential expression of 16 genes coding for cell cycle-and apoptosis-related proteins in vitamin D- induced differentiation of HL-60 cell. Exp Oncol 29:314–316 (2007).
Hofmann, W. K. et al. Altered apoptosis pathways in mantle cell lymphoma detected by oligonucleotide microarray. Blood 98:787–794 (2001).
Kanli, A. & Sacli, H. Differential expression of 16 genes coding for cell cycle-and apoptosis-related proteins in vitamin D- induced differentiation of HL-60 cells. Exp Oncol 29:314–316 (2007).
Hakan, S. et al. Real-time PCR analysis of the apoptosis related genes in ATRA treated patients. Exp Mol Medicine 35:454–459 (2003).
Yoo, W. G. et al. Reference genes for quantitative analysis on Clonorchis sinensis gene expression by real-time PCR. Parasitol Res 104:321–328 (2009).
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Kim, J.Y., Lim, H.S. & Shin, CG. Increased expression of apoptotic genes in cancer cells by heat-processed crude saponin. Mol. Cell. Toxicol. 7, 7–13 (2011). https://doi.org/10.1007/s13273-011-0002-4
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DOI: https://doi.org/10.1007/s13273-011-0002-4