An Atomic Force Microscope Study Revealed Two Mechanisms in the Effect of Anticancer Drugs on Rate-Dependent Young's Modulus of Human Prostate Cancer Cells.
Mechanical properties of cells have been recognized as a biomarker for cellular cytoskeletal organization. As chemical treatments lead to cell cytoskeletal rearrangements, thereby, modifications of cellular mechanical properties, investigating cellular mechanical property variations provides insightful knowledge to effects of chemical treatments on cancer cells. In this study, the effects of eight different anticancer drugs on the mechanical properties of human prostate cancer cell (PC-3) are investigated using a recently developed control-based nanoindentation measurement (CNM) protocol on atomic force microscope (AFM). The CNM protocol overcomes the limits of other existing methods to in-liquid nanoindentation measurement of live cells on AFM, particularly for measuring mechanical properties of live cells. The Young's modulus of PC-3 cells treated by the eight drugs was measured by varying force loading rates over three orders of magnitude, and compared to the values of the control. The results showed that the Young's modulus of the PC-3 cells increased substantially by the eight drugs tested, and became much more pronounced as the force load rate increased. Moreover, two distinct trends were clearly expressed, where under the treatment of Disulfiram, paclitaxel, and MK-2206, the exponent coefficient of the frequency- modulus function remained almost unchanged, while with Celebrex, BAY, Totamine, TPA, and Vaproic acid, the exponential rate was significantly increased.
Department of Mechanical and Aerospace Engineering, Rutgers, the State University of New Jersey, Piscataway, NJ, 08854, USA.
Juan
J
Ren
Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou, 510006, P. R. China.
Huarong
H
Huang
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ, 08854, USA.
Yue
Y
Liu
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ, 08854, USA; Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou, 510006, P. R. China.
Xi
X
Zheng
Department of Mechanical and Aerospace Engineering, Rutgers, the State University of New Jersey, Piscataway, NJ, 08854, USA.
Qingze
Q
Zou
D000596:Amino Acids / Q000494:pharmacology; D000068579:Celecoxib / Q000494:pharmacology; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004221:Disulfiram / Q000494:pharmacology; D055119:Elastic Modulus / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology; D006801:Humans; D008297:Male; D018625:Microscopy, Atomic Force / Q000379:methods*; D008962:Models, Theoretical; D017239:Paclitaxel / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000378:metabolism
D000596:Amino Acids; D006575:Heterocyclic Compounds, 3-Ring; C548887:MK 2206; C019115:totamine; D000068579:Celecoxib; D017239:Paclitaxel; D004221:Disulfiram