Berberine decreases cell growth but increases the side population fraction of H460 lung cancer cells
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Berberine has been reported to inhibit tumor growth in lung cancer. Thus, the effects of berberine on cancer cells as well as the cancer stem cell (side population; SP) fraction were investigated in the H460 lung cancer cell line, and the effects of berberine treatment on cell growth, cell cycle, and cell death were evaluated. Changes in the SP fraction were examined after treatment with berberine, 5-fluorouracil (5-FU), and co-treatment. Berberine inhibited cancer cell growth in a dose-dependent manner. Treatment of the cells with berberine resulted in a 4% increase in cell death and an 8% increase in the number of cells of G0/G1 phase, compared to the untreated control. To examine the relationship between berberine and cancer stem cells, the SP fraction was analyzed. Surprisingly, the SP cell fraction was increased upon berberine treatment and further increased after cotreatment with 5-FU. These results are in contrast to the study of Kim et al. (2008) with MCF-7 breast cancer cells, in which berberine inhibited the growth of both cancer cells and the corresponding cancer stem cells. Results of the present study suggest that berberine should be used with caution in the treatment of various cancers, despite its positive effect on cancer cell growth inhibition.
- Abe K, Shimizu R, Pan X, Hamada H, Yoshikawa H, and Yamamoto M (2009) Stem cells of GATA1-related leukemia undergo pernicious changes after 5-fluorouracil treatment. Exp Hematol 37, 435–445 e431. CrossRef
- Chikazawa N, Tanaka H, Tasaka T, Nakamura M, Tanaka M, Onishi H et al. (2010) Inhibition of Wnt signaling pathway decreases chemotherapyresistant side-population colon cancer cells. Anticancer Res 30, 2041–2048.
- Christgen M, Ballmaier M, Bruchhardt H, von Wasielewski R, Kreipe H, and Lehmann U (2007) Identification of a distinct side population of cancer cells in the Cal-51 human breast carcinoma cell line. Mol Cell Biochem 306, 201–212. CrossRef
- Goodell MA, Brose K, Paradis G, Conner AS, and Mulligan RC (1996) Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 183, 1797–1806. CrossRef
- Haraguchi N, Utsunomiya T, Inoue H, Tanaka F, Mimori K, Barnard GF et al. (2006) Characterization of a side population of cancer cells from human gastrointestinal system. Stem Cells 24, 506–513. CrossRef
- Harper LJ, Piper K, Common J, Fortune F, and Mackenzie IC (2007) Stem cell patterns in cell lines derived from head and neck squamous cell carcinoma. J Oral Pathol Med 36, 594–603. CrossRef
- Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel U et al. (2004) A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA 101, 14228–14233. CrossRef
- Ho YT, Yang JS, Lu CC, Chiang JH, Li TC, Lin JJ et al. (2009) Berberine inhibits human tongue squamous carcinoma cancer tumor growth in a murine xenograft model. Phytomedicine 16, 887–890. CrossRef
- Huang D, Gao Q, Guo L, Zhang C, Jiang W, Li H et al. (2009) Isolation and identification of cancer stem-like cells in esophageal carcinoma cell lines. Stem Cells Dev 18, 465–473. CrossRef
- Jantova S, Letasiova S, Brezova V, Cipak L, and Labaj J (2006) Photochemical and phototoxic activity of berberine on murine fibroblast NIH-3T3 and Ehrlich ascites carcinoma cells. J Photochem Photobiol B 85, 163–176. CrossRef
- Katiyar SK, Meeran SM, Katiyar N, and Akhtar S (2009) p53 Cooperates berberine-induced growth inhibition and apoptosis of non-small cell human lung cancer cells in vitro and tumor xenograft growth in vivo. Mol Carcinog 48, 24–37. CrossRef
- Kim JB, Ko E, Han W, Shin I, Park SY, and Noh DY (2008) Berberine diminishes the side population and ABCG2 transporter expression in MCF-7 breast cancer cells. Planta Med 74, 1693–1700. CrossRef
- Kim JB, Yu JH, Ko E, Lee KW, Song AK, Park SY et al. (2010) The alkaloid berberine inhibits the growth of Anoikis-resistant MCF-7 and MDAMB-231 breast cancer cell lines by inducing cell cycle arrest. Phytomedicine 17, 436–440. CrossRef
- Lee HS, Kim BS, and Kim MK (2002) Suppression effect of Cinnamomum cassia bark-derived component on nitric oxide synthase. J Agric Food Chem 50, 7700–7703. CrossRef
- Leng SH, Lu FE, and Xu LJ (2004) Therapeutic effects of berberine in impaired glucose tolerance rats and its influence on insulin secretion. Acta Pharmacol Sin 25, 496–502.
- Lin CC, Kao ST, Chen GW, Ho HC, and Chung JG (2006) Apoptosis of human leukemia HL-60 cells and murine leukemia WEHI-3 cells induced by berberine through the activation of caspase-3. Anticancer Res 26, 227–242.
- Liu Y, Lou SY, and He YM (2008) Effects of berberine on cell proliferation, peroxisome proliferation activated receptor gamma, CAAT/enhancer binding protein mRNA and protein expression in 3T3-L1 pre-adipocytes. Zhongguo Zhong i Yi Jie He Za Zhi 28, 1005–1009.
- Luo Y, Hao Y, Shi TP, Deng WW, and Li N (2008) Berberine inhibits cyclin D1 expression via suppressed binding of AP-1 transcription factors to CCND1 AP-1 motif. Acta Pharmacol Sin 29, 628–633. CrossRef
- Meng X, Wang X, and Wang Y (2009) More than 45% of A549 and H446 cells are cancer initiating cells: evidence from cloning and tumorigenic analyses. Oncol Rep 21, 995–1000.
- Mimeault M and Batra SK (2009) Characterization of nonmalignant and malignant prostatic stem/progenitor cells by Hoechst side population method. Methods Mol Biol 568, 139–149. CrossRef
- Mitani N, Murakami K, Yamaura T, Ikeda T, and Saiki I (2001) Inhibitory effect of berberine on the mediastinal lymph node metastasis produced by orthotopic implantation of Lewis lung carcinoma. Cancer Lett 165, 35–42. CrossRef
- Oates JE, Grey BR, Addla SK, Samuel JD, Hart CA, Ramani VA et al. (2009) Hoechst 33342 side population identification is a conserved and unified mechanism in urological cancers. Stem Cells Dev 18, 1515–1522. CrossRef
- Pandey MK, Sung B, Kunnumakkara AB, Sethi G, Chaturvedi MM, and Aggarwal BB (2008) Berberine modifies cysteine 179 of IkappaBalpha kinase, suppresses nuclear factor-kappaB-regulated antiapoptotic gene products, and potentiates apoptosis. Cancer Res 68, 5370–5379. CrossRef
- Peng PL, Hsieh YS, Wang CJ, Hsu JL, and Chou FP (2006) Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2. Toxicol Appl Pharmacol 214, 8–15. CrossRef
- Reya T, Morrison SJ, Clarke MF, and Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414, 105–111. CrossRef
- Sauna ZE, Shukla S, and Ambudkar SV (2005) Disulfiram, an old drug with new potential therapeutic uses for human cancers and fungal infections. Mol Biosyst 1, 127–134. CrossRef
- Shen G, Shen F, Shi Z, Liu W, Hu W, Zheng X et al. (2008) Identification of cancer stem-like cells in the C6 glioma cell line and the limitation of current identification methods. In Vitro Cell Dev Biol Anim 44, 280–289. CrossRef
- Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, Dinulescu DM, Connolly D, Foster R et al. (2006) Ovarian cancer side population defines cells with stem cell-like characteristics and mullerian inhibiting substance responsiveness. Proc Natl Acad Sci USA 103, 11154–11159. CrossRef
- Yang M, Zhang R, Yan M, Ye Z, Liang W, and Luo Z (2010) Detection and characterization of side population in Ewing’s sarcoma SK-ES-1 cells in vitro. Biochem Biophys Res Commun 391, 1062–1066. CrossRef
- Yajima T, Ochiai H, Uchiyama T, Takano N, Shibahara T, and Azuma T (2009) Resistance to cytotoxic chemotherapy-induced apoptosis in side population cells of human oral squamous cell carcinoma cell line Ho-1-N-1. Int J Oncol 35, 273–280.
- Berberine decreases cell growth but increases the side population fraction of H460 lung cancer cells
Journal of the Korean Society for Applied Biological Chemistry
Volume 55, Issue 4 , pp 491-495
- Cover Date
- Print ISSN
- Online ISSN
- The Korean Society for Applied Biological Chemistry
- Additional Links
- cancer stem cells
- cell growth
- lung cancer
- side population
- Author Affiliations
- 3. Biomedical Research Institute, Seoul National University Hospital, Seoul, 110-744, Republic of Korea
- 2. Real Cosmetic Surgery Clinic, Asia Building 580 Sinsa-dong, Gangnamgu, Seoul, 152-892, Republic of Korea
- 1. Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, Republic of Korea
- 4. Department of Bioenvironmental Chemistry, College of Agriculture & Life Science, Chonbuk National University, Jeonju, 561-756, Republic of Korea