Summary
The aim of this study was to evaluate the biological activity and pharmacological activity of several amphiphilic liquid-crystalline compounds (LCs), i.e. phenylpyrimidine derivatives possessing D-glucamine and cyanobiphenyl derivatives with a terminal hydroxyl unit, to explore novel anti-cancer functions of the LCs. The anti-cancer properties of the LCs were investigated in A549 human lung cancer cells by assessing cell growth, cell cycle distribution, and cell signaling pathways using a flow cytometer and a Western blot analysis. In addition, the effect of LCs on the growth of WI-38 normal fibroblasts was examined. Consequently, the phenylpyrimidine derivatives and cyanobiphenyl derivatives showed cytostatic effects, causing the suppression of cell growth through G1 phase arrest in A549 cells. Further analyses using phenylpyrimidine derivatives and precursors of a cyanobiphenyl compound demonstrated the structure-activity relationships. One of the phenylpyrimidine derivatives inhibited A549 growth without any toxicity to normal fibroblasts. As a result, a novel pharmacological function was hypothesized to be inherent in the structure of the LCs themselves, and the dependence of the tumor-specific activity on the hydrophobic group of phenylpyrimidine derivatives therefore remains an interesting issue. Our results suggest the possibility that the LCs themselves may act as a novel type of chemotherapeutic agent.
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References
Kuo PL, Hsu YL, Lin TC, Chang JK (2005) Induction of cell cycle arrest and apoptosis in human non-small cell lung cancer A549 cells by casuarinin from the bark of Terminalia arjuna Linn. Anticancer Drugs 4:409–415
Abe A, Yamane M, Tomoda A (2001) Prevention of growth of human lung carcinoma cells and induction of apoptosis by a novel phenoxazinone, 2-amino-4, 4[alpha]-dihydro-4[alpha], 7-dimethyl-3H-phenoxazine-3-one. Anticancer Drugs 12:377–382
Tang N, Du G, Wang N, Liu C, Hang H, Liang W (2007) Improving penetration in tumors with nanoassemblies of phospholipids and doxorubicin. J Natl Cancer Inst 99:1004–1015
Chang JH, Hung CF, Yang SC, Wang JP, Won SJ, Lin CN (2008) Synthesis and cytotoxic, anti-inflammatory, and anti-oxidant activities of 2′,5′-dialkoxylchalcones as cancer chemopreventive agents. Bioorg Med Chem 16:7270–7276
Goel A, Prasad AK, Parmar VS, Ghosh B, Saini N (2007) 7, 8-Dihydroxy-4-methylcoumarin induces apoptosis of human lung adenocarcinoma cells by ROS-independent mitochondrial pathway through partial inhibition of ERK/MAPK signaling. FEBS Lett 581:2447–2454
Chou TC, Zhang X, Zhong ZY, Li Y, Feng L, Eng S, Myles DR, Johnson R, Wu N, Yin YI, Wilson RM, Danishefsky SJ (2008) Therapeutic effect against human xenograft tumors in nude mice by the third generation microtubule stabilizing epothilones. Proc Natl Acad Sci 35:13157–13162
Zhang JH, Fan CD, Zhao BX, Shin DS, Dong WL, Xie YS, Miao JY (2008) Synthesis and preliminary biological evaluation of novel pyrazolo[1, 5-a] pyrazin-4(5H)-one derivatives aspotential agents against A549 lung cancer cells. Bioorg Med Chem 16:10165–10171
Goodby JW, Görtz V, Cowling SJ, Mackenzie G, Martin P, Plusquellec D, Benvegnu T, Boullanger P, Lafont D, Queneau Y, Chambert S, Fitremann J (2007) Thermotropic liquid crystalline glycolipids. Chem Soc Rev 36:1971–2032
Luk YY, Campbell SF, Abbott NL, Murphy CJ (2004) Non-toxic thermotropic liquid crystals for use with mammalian cells. Liquid Cryst 31:611–621
Cervin C, Vandoolaeghe P, Nistor C, Tiberg F, Johnsson M (2009) A combined in vitro and in vivo study on the interactions between somatostatin and lipid-based liquid crystalline drug carriers and bilayers. Eur J Pharm Sci 36:377–385
Yoshizawa A, Takahashi Y, Nishizawa A, Takeuchi K, Sagisaka M, Takahasi K, Hazawa M, Kashiwakura I (2009) Liquid crystallinity and biological activity of a novel amphiphilic compound. Chem Lett 38:310–311
Yoshizawa A, Takahashi Y, Nishizawa A, Takeuchi K, Sagisaka M, Takahasi K, Hazawa M, Kashiwakura I (2009) Biological activity of some cyanobiphenyl derivatives. Chem Lett 38:530–531
Hosseinimehr JS, Inanami O, Hamasu T, Takahashi M, Kashiwakura I, Asanuma T, Kuwabara M (2004) Activation of c-kit by stem cell factor induces radioresistance to apoptosis through ERK-dependent expression of survivin in HL60 cells. J Radiat Res 45:557–561
Liu Y, Nakahara T, Miyakoshi J, Hu DL, Nakane A, Abe Y (2007) Nuclear accumulation and activation of nuclear factor κB after split-dose irradiation in LS174T cells. J Radiat Res 48:13–20
Tschierske C (2007) Liquid crystal engineering-new complex mesophase structures and their relations to polymer morphologies, nanoscale patterning and crystal engineering. Chem Soc Rev 36:1930–1970
Lee JW, Min HY, Han AR, Chung HJ, Park EJ, Park HJ, Hong JY, Seo EK, Lee SK (2007) Growth inhibition and induction of G1 phase cell cycle arrest in human lung cancer cells by a phenylbutenoid dimer isolated from Zingiber cassumunar. Biol Pharm Bull 30:1561–1564
Nguyen TT, Tran E, Ong CK, Lee SK, Do PT, Huynh TT, Nguyen TH, Lee JJ, Tan Y, Ong CS, Huynh H (2003) Kaempferol-induced growth inhibition and apoptosis in A549 lung carcinoma cells is mediated by activation of MEK-MAPK. J Cell Physiol 197:110–121
Ogura H, Tsukumo Y, Sugimoto H, Igarashi M, Nagai K, Kataoka T (2008) ERK and p38 MAP kinase are involved in downregulation of cell surface TNF receptor 1 induced by acetoxycycloheximide. Int Immunopharmacol 8:922–926
Yano Y, Satoh H, Fukumoto K, Kumadaki I, Ichikawa T, Yamada K, Hagiwara K, Yano T (2005) Induction of cytotoxicity in human lung adenocarcinoma cells by 6-O-carboxypropyl-alpha-tocotrienol, a redox-silent derivative of alpha-tocotrienol. Int J Cancer 115:839–846
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This study was supported by a Grant for Hirosaki University Institutional Research (2008–2009) and by a Grant-in-Aid for Challenging Exploratory Research from Japan Society for the Promotion of Science (No. 21655045).
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Takahashi, Y., Hazawa, M., Takahashi, K. et al. Suppressive effects of liquid crystal compounds on the growth of the A549 human lung cancer cell line. Invest New Drugs 29, 659–665 (2011). https://doi.org/10.1007/s10637-010-9411-9
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DOI: https://doi.org/10.1007/s10637-010-9411-9