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BioMed Research International
Volume 2015 (2015), Article ID 430569, 14 pages
Research Article

Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

1Biotechnology Program, School of Sciences and Engineering, The American University in Cairo, AUC Avenue, New Cairo 11835, Egypt
2Department of Biology, School of Sciences and Engineering, The American University in Cairo, AUC Avenue, New Cairo 11835, Egypt
3Department of Mechanical and Industrial Engineering, Ryerson University, 350 Victoria Street, Toronto, ON, Canada M5B 2K3
4Martin Orthopaedic Biomechanics Lab, St. Michael’s Hospital, 209 Victoria Street, Toronto, ON, Canada M5B 1W8
5Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON, Canada M5S 3G8

Received 13 June 2014; Revised 18 September 2014; Accepted 13 October 2014

Academic Editor: Vickram Ramkumar

Copyright © 2015 Laila Ziko et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Cisplatin (CisPt) is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2) cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death). Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death).