Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

Author:

Ziko Laila1ORCID,Riad Sandra2,Amer Momen1ORCID,Zdero Radovan345ORCID,Bougherara Habiba3,Amleh Asma12ORCID

Affiliation:

1. Biotechnology Program, School of Sciences and Engineering, The American University in Cairo, AUC Avenue, New Cairo 11835, Egypt

2. Department of Biology, School of Sciences and Engineering, The American University in Cairo, AUC Avenue, New Cairo 11835, Egypt

3. Department of Mechanical and Industrial Engineering, Ryerson University, 350 Victoria Street, Toronto, ON, Canada M5B 2K3

4. Martin Orthopaedic Biomechanics Lab, St. Michael’s Hospital, 209 Victoria Street, Toronto, ON, Canada M5B 1W8

5. Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON, Canada M5S 3G8

Abstract

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).

Funder

Natural Sciences and Engineering Research Council of Canada

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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