title: Mechanical stress promotes cisplatin-induced hepatocellular carcinoma cell death.
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).
authors: Biotechnology Program, School of Sciences and Engineering, The American University in Cairo, AUC Avenue, New Cairo 11835, Egypt.
authors: Laila
authors: 0000-0003-1364-8255
authors: L
authors: Ziko
authors: Department of Biology, School of Sciences and Engineering, The American University in Cairo, AUC Avenue, New Cairo 11835, Egypt.
authors: Sandra
authors: S
authors: Riad
authors: Biotechnology Program, School of Sciences and Engineering, The American University in Cairo, AUC Avenue, New Cairo 11835, Egypt.
authors: Momen
authors: 0000-0002-5030-2504
authors: M
authors: Amer
authors: Department of Mechanical and Industrial Engineering, Ryerson University, 350 Victoria Street, Toronto, ON, Canada M5B 2K3 ; Martin Orthopaedic Biomechanics Lab, St. Michael's Hospital, 209 Victoria Street, Toronto, ON, Canada M5B 1W8 ; Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON, Canada M5S 3G8.
authors: Radovan
authors: 0000-0003-0853-3402
authors: R
authors: Zdero
authors: Department of Mechanical and Industrial Engineering, Ryerson University, 350 Victoria Street, Toronto, ON, Canada M5B 2K3.
authors: Habiba
authors: H
authors: Bougherara
authors: Biotechnology Program, School of Sciences and Engineering, The American University in Cairo, AUC Avenue, New Cairo 11835, Egypt ; Department of Biology, School of Sciences and Engineering, The American University in Cairo, AUC Avenue, New Cairo 11835, Egypt.
authors: Asma
authors: 0000-0003-3613-3182
authors: A
authors: Amleh
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D016923:Cell Death / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008954:Models, Biological; D013314:Stress, Mechanical
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin