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Published in: Digestive Diseases and Sciences 8/2011

01-08-2011 | Original Article

Differentiation-Inducing Activity of Hydroxycamptothecin on Cancer Stem-Like Cells Derived from Hepatocellular Carcinoma

Authors: Yi Zhang, Wen-Jie Song, Fu-Qin Zhang, Wei-Hui Liu, Ke-Feng Dou

Published in: Digestive Diseases and Sciences | Issue 8/2011

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Abstract

Background

Hydroxycamptothecin (HCPT) is an anti-tumor agent that can induce differentiation in human cancer cells. Recent evidence indicates that side population (SP) cells possess characteristics of stem-like cells, and may be capable of initiating tumor growth.

Aims

The present study investigated the differentiation of cancer stem-like cells derived from hepatocellular carcinoma.

Methods and Results

Flow cytometry was used to isolated SP cells from HCC cell line (MHCC97 cells). These SP cells exhibit several stem-like cell characteristics that are distinct from the main population (MP) cells in vitro. After 3 days of induction with a low concentration of HCPT, the SP cells lost their capacity to proliferate and invade, and their tumorigenicity declined. Based on real-time quantitative RT-PCR, we also found that the expression of hepatocyte-specific markers such as α-fetoprotein, albumin, hepatocyte nuclear factor-4 and miR-122 gradually changed during the differentiation of SP cells.

Conclusions

Our data suggest that a low concentration of HCPT can induce hepatocyte-specific differentiation of cancer stem-like cells from MHCC97 cells, offering a possible therapeutic strategy for the treatment of human malignancies.
Literature
2.
4.
go back to reference Vermeulen L, Sprick MR, Kemper K, Stassi G, Medema JP. Cancer stem cells—old concepts, new insights. Cell Death Differ. 2008;15:947–958.PubMedCrossRef Vermeulen L, Sprick MR, Kemper K, Stassi G, Medema JP. Cancer stem cells—old concepts, new insights. Cell Death Differ. 2008;15:947–958.PubMedCrossRef
5.
go back to reference Ma S, Chan KW, Hu L, et al. Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology. 2007;132:2542–2556.PubMedCrossRef Ma S, Chan KW, Hu L, et al. Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology. 2007;132:2542–2556.PubMedCrossRef
6.
go back to reference Hussain SZ, Strom SC, Kirby MR, et al. Side population cells derived from adult human liver generate hepatocyte-like cells in vitro. Dig Dis Sci. 2005;50:1755–1763.PubMedCrossRef Hussain SZ, Strom SC, Kirby MR, et al. Side population cells derived from adult human liver generate hepatocyte-like cells in vitro. Dig Dis Sci. 2005;50:1755–1763.PubMedCrossRef
7.
go back to reference Ho MM, Ng AV, Lam S, Hung JY. Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res. 2007;67:4827–4833.PubMedCrossRef Ho MM, Ng AV, Lam S, Hung JY. Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res. 2007;67:4827–4833.PubMedCrossRef
8.
go back to reference Harris MA, Yang H, Low BE, et al. Cancer stem cells are enriched in the side population cells in a mouse model of glioma. Cancer Res. 2008;68:10051–10059.PubMedCrossRef Harris MA, Yang H, Low BE, et al. Cancer stem cells are enriched in the side population cells in a mouse model of glioma. Cancer Res. 2008;68:10051–10059.PubMedCrossRef
9.
go back to reference Chiba T, Kita K, Zheng YW, et al. Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology. 2006;44:240–251.PubMedCrossRef Chiba T, Kita K, Zheng YW, et al. Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology. 2006;44:240–251.PubMedCrossRef
11.
go back to reference Lin TL, Vala MS, Barber JP, et al. Induction of acute lymphocytic leukemia differentiation by maintenance therapy. Leukemia. 2007;21:1915–1920.PubMedCrossRef Lin TL, Vala MS, Barber JP, et al. Induction of acute lymphocytic leukemia differentiation by maintenance therapy. Leukemia. 2007;21:1915–1920.PubMedCrossRef
12.
go back to reference Waxman S. Differentiation therapy in acute myelogenous leukemia (non-apl). Leukemia. 2000;14:491–496.PubMedCrossRef Waxman S. Differentiation therapy in acute myelogenous leukemia (non-apl). Leukemia. 2000;14:491–496.PubMedCrossRef
13.
go back to reference Kawamata H, Tachibana M, Fujimori T, Imai Y. Differentiation-inducing therapy for solid tumors. Curr Pharm Des. 2006;12:379–385.PubMedCrossRef Kawamata H, Tachibana M, Fujimori T, Imai Y. Differentiation-inducing therapy for solid tumors. Curr Pharm Des. 2006;12:379–385.PubMedCrossRef
14.
go back to reference Kondo K, Tsuneizumi K, Watanabe T, Oishi M. Induction of in vitro differentiation of mouse embryonal carcinoma (f9) cells by inhibitors of topoisomerases. Cancer Res. 1991;51:5398–5404.PubMed Kondo K, Tsuneizumi K, Watanabe T, Oishi M. Induction of in vitro differentiation of mouse embryonal carcinoma (f9) cells by inhibitors of topoisomerases. Cancer Res. 1991;51:5398–5404.PubMed
15.
go back to reference Jing Y, Hashimoto S, Nakajo S, Nakaya K. Topoisomerase inhibitors potentiate the effect of retinoic acid on cell growth inhibition and induction of differentiation of leukemia hl-60 cells. Leuk Res. 1994;18:299–304.PubMedCrossRef Jing Y, Hashimoto S, Nakajo S, Nakaya K. Topoisomerase inhibitors potentiate the effect of retinoic acid on cell growth inhibition and induction of differentiation of leukemia hl-60 cells. Leuk Res. 1994;18:299–304.PubMedCrossRef
16.
go back to reference Santos A, Calvet L, Terrier-Lacombe MJ, et al. In vivo treatment with cpt-11 leads to differentiation of neuroblastoma xenografts and topoisomerase i alterations. Cancer Res. 2004;64:3223–3229.PubMedCrossRef Santos A, Calvet L, Terrier-Lacombe MJ, et al. In vivo treatment with cpt-11 leads to differentiation of neuroblastoma xenografts and topoisomerase i alterations. Cancer Res. 2004;64:3223–3229.PubMedCrossRef
17.
go back to reference Kamiya A, Gonzalez FJ, Nakauchi H. Identification and differentiation of hepatic stem cells during liver development. Front Biosci. 2006;11:1302–1310.PubMedCrossRef Kamiya A, Gonzalez FJ, Nakauchi H. Identification and differentiation of hepatic stem cells during liver development. Front Biosci. 2006;11:1302–1310.PubMedCrossRef
18.
go back to reference van der Zee AG, de Jong S, Keith WN, et al. Quantitative and qualitative aspects of topoisomerase i and ii alpha and beta in untreated and platinum/cyclophosphamide treated malignant ovarian tumors. Cancer Res. 1994;54:749–755.PubMed van der Zee AG, de Jong S, Keith WN, et al. Quantitative and qualitative aspects of topoisomerase i and ii alpha and beta in untreated and platinum/cyclophosphamide treated malignant ovarian tumors. Cancer Res. 1994;54:749–755.PubMed
19.
go back to reference Boonsong A, Curran S, McKay JA, et al. Topoisomerase i protein expression in primary colorectal cancer and lymph node metastases. Hum Pathol. 2002;33:1114–1119.PubMedCrossRef Boonsong A, Curran S, McKay JA, et al. Topoisomerase i protein expression in primary colorectal cancer and lymph node metastases. Hum Pathol. 2002;33:1114–1119.PubMedCrossRef
20.
go back to reference Gouveris P, Lazaris AC, Papathomas TG, et al. Topoisomerase i protein expression in primary colorectal cancer and recurrences after 5-fu-based adjuvant chemotherapy. J Cancer Res Clin Oncol. 2007;133:1011–1015.PubMedCrossRef Gouveris P, Lazaris AC, Papathomas TG, et al. Topoisomerase i protein expression in primary colorectal cancer and recurrences after 5-fu-based adjuvant chemotherapy. J Cancer Res Clin Oncol. 2007;133:1011–1015.PubMedCrossRef
21.
go back to reference Ling YH, Tseng MT, Nelson JA. Differentiation induction of human promyelocytic leukemia cells by 10-hydroxycamptothecin, a DNA topoisomerase i inhibitor. Differentiation. 1991;46:135–141.PubMedCrossRef Ling YH, Tseng MT, Nelson JA. Differentiation induction of human promyelocytic leukemia cells by 10-hydroxycamptothecin, a DNA topoisomerase i inhibitor. Differentiation. 1991;46:135–141.PubMedCrossRef
22.
go back to reference Zhang XW, Jiang JF, Xu B. Differentiation-inducing action of 10- hydroxycamptothecin on human hepatoma hep g2 cells. Acta Pharmacol Sin. 2000;21:364–368.PubMed Zhang XW, Jiang JF, Xu B. Differentiation-inducing action of 10- hydroxycamptothecin on human hepatoma hep g2 cells. Acta Pharmacol Sin. 2000;21:364–368.PubMed
23.
go back to reference Hirschmann-Jax C, Foster AE, Wulf GG, et al. A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA. 2004;101:14228–14233.PubMedCrossRef Hirschmann-Jax C, Foster AE, Wulf GG, et al. A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA. 2004;101:14228–14233.PubMedCrossRef
24.
go back to reference Wu C, Wei Q, Utomo V, et al. Side population cells isolated from mesenchymal neoplasms have tumor initiating potential. Cancer Res. 2007;67:8216–8222.PubMedCrossRef Wu C, Wei Q, Utomo V, et al. Side population cells isolated from mesenchymal neoplasms have tumor initiating potential. Cancer Res. 2007;67:8216–8222.PubMedCrossRef
25.
go back to reference Shackleton M. Normal stem cells and cancer stem cells: similar and different. Semin Cancer Biol. 2010;20:85–92.PubMedCrossRef Shackleton M. Normal stem cells and cancer stem cells: similar and different. Semin Cancer Biol. 2010;20:85–92.PubMedCrossRef
26.
go back to reference Fulda S, Pervaiz S. Apoptosis signaling in cancer stem cells. Int J Biochem Cell Biol. 2010;42:31–38.PubMedCrossRef Fulda S, Pervaiz S. Apoptosis signaling in cancer stem cells. Int J Biochem Cell Biol. 2010;42:31–38.PubMedCrossRef
27.
go back to reference Gilbert CA, Ross AH. Cancer stem cells: cell culture, markers, and targets for new therapies. J Cell Biochem. 2009;108:1031–1038.PubMedCrossRef Gilbert CA, Ross AH. Cancer stem cells: cell culture, markers, and targets for new therapies. J Cell Biochem. 2009;108:1031–1038.PubMedCrossRef
28.
29.
go back to reference Patrawala L, Calhoun T, Schneider-Broussard R, et al. Side population is enriched in tumorigenic, stem-like cancer cells, whereas abcg2+ and abcg2− cancer cells are similarly tumorigenic. Cancer Res. 2005;65:6207–6219.PubMedCrossRef Patrawala L, Calhoun T, Schneider-Broussard R, et al. Side population is enriched in tumorigenic, stem-like cancer cells, whereas abcg2+ and abcg2− cancer cells are similarly tumorigenic. Cancer Res. 2005;65:6207–6219.PubMedCrossRef
30.
go back to reference Hu C, Li H, Li J, et al. Analysis of abcg2 expression and side population identifies intrinsic drug efflux in the hcc cell line mhcc-97l and its modulation by akt signaling. Carcinogenesis. 2008;29:2289–2297.PubMedCrossRef Hu C, Li H, Li J, et al. Analysis of abcg2 expression and side population identifies intrinsic drug efflux in the hcc cell line mhcc-97l and its modulation by akt signaling. Carcinogenesis. 2008;29:2289–2297.PubMedCrossRef
31.
go back to reference Polgar O, Robey RW, Bates SE. Abcg2: structure, function and role in drug response. Expert Opin Drug Metab Toxicol. 2008;4:1–15.PubMedCrossRef Polgar O, Robey RW, Bates SE. Abcg2: structure, function and role in drug response. Expert Opin Drug Metab Toxicol. 2008;4:1–15.PubMedCrossRef
32.
go back to reference Chen Z, Liu F, Ren Q, et al. Suppression of abcg2 inhibits cancer cell proliferation. Int J Cancer. 2010;126:841–851.PubMed Chen Z, Liu F, Ren Q, et al. Suppression of abcg2 inhibits cancer cell proliferation. Int J Cancer. 2010;126:841–851.PubMed
33.
go back to reference Wilkening S, Stahl F, Bader A. Comparison of primary human hepatocytes and hepatoma cell line hepg2 with regard to their biotransformation properties. Drug Metab Dispos. 2003;31:1035–1042.PubMedCrossRef Wilkening S, Stahl F, Bader A. Comparison of primary human hepatocytes and hepatoma cell line hepg2 with regard to their biotransformation properties. Drug Metab Dispos. 2003;31:1035–1042.PubMedCrossRef
34.
go back to reference Jones EA, Clement-Jones M, James OF, Wilson DI. Differences between human and mouse alpha-fetoprotein expression during early development. J Anat. 2001;198:555–559.PubMedCrossRef Jones EA, Clement-Jones M, James OF, Wilson DI. Differences between human and mouse alpha-fetoprotein expression during early development. J Anat. 2001;198:555–559.PubMedCrossRef
35.
go back to reference Li J, Ning G, Duncan SA. Mammalian hepatocyte differentiation requires the transcription factor hnf-4alpha. Genes Dev. 2000;14:464–474.PubMed Li J, Ning G, Duncan SA. Mammalian hepatocyte differentiation requires the transcription factor hnf-4alpha. Genes Dev. 2000;14:464–474.PubMed
36.
go back to reference Herbst RS, Nielsch U, Sladek F, et al. Differential regulation of hepatocyte-enriched transcription factors explains changes in albumin and transthyretin gene expression among hepatoma cells. New Biol. 1991;3:289–296.PubMed Herbst RS, Nielsch U, Sladek F, et al. Differential regulation of hepatocyte-enriched transcription factors explains changes in albumin and transthyretin gene expression among hepatoma cells. New Biol. 1991;3:289–296.PubMed
37.
go back to reference Bai S, Nasser MW, Wang B, et al. Microrna-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib. J Biol Chem. 2009;284:32015–32027.PubMedCrossRef Bai S, Nasser MW, Wang B, et al. Microrna-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib. J Biol Chem. 2009;284:32015–32027.PubMedCrossRef
38.
go back to reference Coulouarn C, Factor VM, Andersen JB, Durkin ME, Thorgeirsson SS. Loss of mir-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene. 2009;28:3526–3536.PubMedCrossRef Coulouarn C, Factor VM, Andersen JB, Durkin ME, Thorgeirsson SS. Loss of mir-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene. 2009;28:3526–3536.PubMedCrossRef
Metadata
Title
Differentiation-Inducing Activity of Hydroxycamptothecin on Cancer Stem-Like Cells Derived from Hepatocellular Carcinoma
Authors
Yi Zhang
Wen-Jie Song
Fu-Qin Zhang
Wei-Hui Liu
Ke-Feng Dou
Publication date
01-08-2011
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 8/2011
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-011-1601-6

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