Am J Cancer Res 2013;3(3):266-277
Original Article
Arginine-conjugated albumin microspheres inhibits proliferation and migration
in lung cancer cells
Hung-Yen Lee, Kamal A Mohammed, Eugene P Goldberg, Najmunnisa Nasreen
Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, NF/SGVHS, Malcom Randall VA Medical Center,
University of Florida, P. O. Box 100225, Biomaterials Center, Department of Materials Sciences and Engineering, University of
Florida, P. O. Box 116400, Gainesville, FL 32611-6400, USA
Received April 2, 2013; Accepted May 20, 2013; Epub June 20, 2013; Published June 30, 2013
Abstract: Arginine is one of the essential amino acid involved in numerous biosynthetic pathways that significantly influence
tumor growth. It has been demonstrated that arginine is effective to inhibit proliferation of cancer cells when an appropriate dose
is applied. Generally, induction of cell death requires high concentration of arginine while low concentration of arginine facilitates
cell proliferation. In addition to the apoptosis induced by metabolism of arginine, it has also been reported that in an ideal
solution environment, arginine may assemble into arginine clusters to kill cancer cells. Therefore, to make the arginine an
effective anticancer agent, arginine/albumin microspheres were designed and synthesized to provide a localized high
concentration of arginine on tumor sites. In addition, the arginine/albumin mesospheres (AAMS) are also expected to provide an
arginine-rich surface on microspheres, which is similar to the arginine cluster, to effectively inhibit tumor growth. In this study, the
AAMS were synthesized through a water/organic solvent emulsion system and the surface properties were characterized. The in
vitro effects of AAMS on A549, CRL-2081, MAK9 lung cancer cells (LCC) proliferation, migration, and tumor growth were
determined. The expression of oncogenic protein EphA2 and transcription factor slug was also determined. AAMS significantly
inhibited the cell proliferation, cell migration and tumor growth in all the three LCC, while same concentration of free arginine
promoted the LCC tumor growth and migration. Our studies indicate that the synthesized AAMS has a more effective inhibiting
effect on proliferation, migration and tumor growth of LCC than freely released arginine. The expression of EphA2 receptor
mRNA was significantly decreased when compared to control cells. In addition the mRNA expression of transcription factor slug
was also inhibited by AAMS suggesting that AAMS affects the expression of EphA2 and slug and may regulate LCC proliferation
and migration. These data suggests that the AAMS can be an ideal delivery vehicle for therapeutic interventions against LCCs.
(ajcr0000195).
Keywords: Arginine-conjugated albumin, microspheres, inhibition, proliferation, migration, lung cancer
Address correspondence to: Dr. Najmunnisa Nasreen, Division of Pulmonary, Critical Care & Sleep Medicine, Department of
Medicine, University of Florida, Gainesville, FL 32601, USA. Phone: 352-376-1611 ext. 6491; Fax: 352-392-7088; E-mail:
nnasreen@medicine.ufl.edu
Original Article
Arginine-conjugated albumin microspheres inhibits proliferation and migration
in lung cancer cells
Hung-Yen Lee, Kamal A Mohammed, Eugene P Goldberg, Najmunnisa Nasreen
Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, NF/SGVHS, Malcom Randall VA Medical Center,
University of Florida, P. O. Box 100225, Biomaterials Center, Department of Materials Sciences and Engineering, University of
Florida, P. O. Box 116400, Gainesville, FL 32611-6400, USA
Received April 2, 2013; Accepted May 20, 2013; Epub June 20, 2013; Published June 30, 2013
Abstract: Arginine is one of the essential amino acid involved in numerous biosynthetic pathways that significantly influence
tumor growth. It has been demonstrated that arginine is effective to inhibit proliferation of cancer cells when an appropriate dose
is applied. Generally, induction of cell death requires high concentration of arginine while low concentration of arginine facilitates
cell proliferation. In addition to the apoptosis induced by metabolism of arginine, it has also been reported that in an ideal
solution environment, arginine may assemble into arginine clusters to kill cancer cells. Therefore, to make the arginine an
effective anticancer agent, arginine/albumin microspheres were designed and synthesized to provide a localized high
concentration of arginine on tumor sites. In addition, the arginine/albumin mesospheres (AAMS) are also expected to provide an
arginine-rich surface on microspheres, which is similar to the arginine cluster, to effectively inhibit tumor growth. In this study, the
AAMS were synthesized through a water/organic solvent emulsion system and the surface properties were characterized. The in
vitro effects of AAMS on A549, CRL-2081, MAK9 lung cancer cells (LCC) proliferation, migration, and tumor growth were
determined. The expression of oncogenic protein EphA2 and transcription factor slug was also determined. AAMS significantly
inhibited the cell proliferation, cell migration and tumor growth in all the three LCC, while same concentration of free arginine
promoted the LCC tumor growth and migration. Our studies indicate that the synthesized AAMS has a more effective inhibiting
effect on proliferation, migration and tumor growth of LCC than freely released arginine. The expression of EphA2 receptor
mRNA was significantly decreased when compared to control cells. In addition the mRNA expression of transcription factor slug
was also inhibited by AAMS suggesting that AAMS affects the expression of EphA2 and slug and may regulate LCC proliferation
and migration. These data suggests that the AAMS can be an ideal delivery vehicle for therapeutic interventions against LCCs.
(ajcr0000195).
Keywords: Arginine-conjugated albumin, microspheres, inhibition, proliferation, migration, lung cancer
Address correspondence to: Dr. Najmunnisa Nasreen, Division of Pulmonary, Critical Care & Sleep Medicine, Department of
Medicine, University of Florida, Gainesville, FL 32601, USA. Phone: 352-376-1611 ext. 6491; Fax: 352-392-7088; E-mail:
nnasreen@medicine.ufl.edu
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American Journal of Cancer Research
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