Tryptone-stabilized gold nanoparticles target tubulin and inhibit cell viability by inducing an unusual form of cell cycle arrest

• Published in: Experimental cell research Vol. 360; no. 2; pp. 163 - 170
• Main Authors: Mahaddalkar, Tejashree, Mehta, Sourabh, Cheriyamundath, Sanith, Muthurajan, Harries, Lopus, Manu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.11.2017
• Subjects: Animals; Apoptosis - drug effects; Cancer; Cell cycle; Cell Cycle - drug effects; Cell Cycle Checkpoints - drug effects; Cell Line, Tumor; Cell Survival - drug effects; Drug Stability; Gold - chemistry; Gold - pharmacology; Gold nanoparticles; HeLa Cells; Humans; Metal Nanoparticles - chemistry; Mice; Microtubules; Molecular Targeted Therapy - methods; NIH 3T3 Cells; Peptones - chemistry; Peptones - pharmacology; Tryptone; TsAuNPs; Tubulin; Tubulin - drug effects; Tubulin - metabolism; Tubulin Modulators - chemistry; Tubulin Modulators - pharmacology; Tryptone; Tubulin; Gold nanoparticles; Microtubules; Cell cycle; TsAuNPs; Cancer
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2017.09.002

Gold nanoparticles have been investigated extensively for their molecular mechanisms of action and anticancer potential. We report a novel, tubulin-targeted antiproliferative mechanism of action of tryptone-stabilized gold nanoparticles (TsAuNPs). TsAuNPs, synthesized using HAuCl4·3H2O and tryptone and characterized by a variety of spectroscopic methods and transmission electron microscopy, were found to be inhibitory to viability of human pancreatic (PANC-1), cervical (HeLa), and breast (MDA-MB-231) cancer cell lines in a concentration-dependent manner, with highest efficacy against PANC-1 cells. The particles strongly inhibited the clonogenic propagation of PANC-1 cells. TsAuNPs-mediated inhibition of cell viability involved an unusual mode of cell cycle arrest (arrest at both G0/G1 phase and S-phase) followed by apoptosis. In vitro, TsAuNPs bound purified tubulin, competitively inhibited anilinonaphthalene sulfonate binding to tubulin, and suppressed tubulin assembly. In cells, tubulin-TsAuNPs interactions were manifested as a disrupted microtubule network, defective reassembly of cold-disassembled microtubules, and induction of tubulin acetylation. Our data indicate that TsAuNPs inhibit cell viability by inducing differential cell cycle arrest possibly through disrupted dynamicity of cellular microtubules. [Display omitted] •TsAuNPs were synthesized using HAuCl4·3H2O and tryptone.•TsAuNPs bound tubulin, promoted its acetylation, and inhibited its reassembly in cells.•TsAuNPs induced G0/G1 and S-phase arrests.•The cells, thus arrested, eventually underwent programmed cell death.•Combining TsAuNPs with a G2/M blocker might be a potential cancer therapeutic strategy.