Alteration of protein and gene expressions of Hexokinase II in PC3 cell lines by cisplatinmetformin combination treatment

2018-07-01
Durukan, Özlem
Akkulak, Merve
Evin, Emre
Arslan, Şevki
Adalı, Orhan
Metformin is an antidiabetic drug with anticancer properties. Cisplatin is known as one of the most potent chemotherapeutics for treatment of various types of cancer. In order to overcome cisplatin resistance and toxicity, the drug can be combined with other drugs that sensitize tumour cells to cisplatin. The ability of metformin to potentiate cisplatin-mediated killing of cancer cells in vitro, makes it a plausible candidate for combination with cisplatin- based therapy. The aim of this study is to examine the combined effect of these drugs on protein and mRNA expressions of Hexokinase II, a regulatory enzyme participating in glycolysis as well as cancer promotion. The effects of drugs on prostate cancer cell lines were studied using androgen independent PC3 cell line. Cells were treated with either metformin alone in the range of 1–10 mM, cisplatin alone or a combination of these two drugs. Cytotoxicity of drugs were determined with Alamar Blue Assay and IC50 was calculated. The effects of drugs on Hexokinase II mRNA and protein expressions were determined by qRT-PCR and western immunoblotting techniques, respectively. The intensity of each band was analyzed by Image J software program. IC50 value of cisplatin on PC3 cell line was found as 30 lM. Both alone or combination of drugs were inhibited the proliferation of PC3 cells in a concentration dependent manner. Hexokinase II mRNA and protein expressions were significantly downregulated in metformin/cisplatin treated cells compared to control groups. Epidemiological and experimental researches indicates that men with abdominal obesity is a risk factor for prostate cancer. Parallel with our results, the adjuvant role of this type of antidiabetic drug must be investigated for new cancer treatment options.

Suggestions

Metformin – Cisplatin Combination Treatment Alters mRNA Expression of Hexokinase II Gene in LNCaP and PC3 Prostate Cancer Cell Lines
Durukan, Özlem; Evin, Emre; Arslan, Şevki; Adalı, Orhan (null; 2017-07-08)
Metformin is an antidiabetic drug with anticancer properties. Cisplatin is known as one of the most potent chemotherapeutics for treatment of various types of cancer. In order to overcome cisplatin resistance and toxicity, the drug can be combined with other chemotherapeutics that sensitize tumour cells to cisplatin. The ability of metformin to potentiate cisplatin-mediated killing of cancer cells in vitro, makes it a plausible candidate for combination with cisplatin-based therapy. The aim of this study is...
Interaction of the cholesterol reducing agent simvastatin with zwitterionic DPPC and charged DPPG phospholipid membranes
Sariisik, Ediz; KOÇAK, MUSTAFA; Baloglu, Fatma Kucuk; Severcan, Feride (Elsevier BV, 2019-04-01)
Simvastatin is a lipid-lowering drug in the pharmaceutical group statins. Interaction of a drug with lipids may define its role in the system and be critical for its pharmacological activity. We examined the interactions of simvastatin with zwitterionic dipalmitoyl phosphatidylcholine (DPPC) and anionic dipalmitoyl phosphatidylglycerol (DPPG) multilamellar vesicles (MLVs) as a function of temperature at different simvastatin concentrations using Fourier transform infrared (FTIR) spectroscopy and differentia...
Alterations of hypothalamic neuropeptides involved in food intake and appetite in olanzapine monotherapy
Sezlev, Deniz; Yanık, Tülin; Department of Biology (2012)
The mechanism of weight gain due to treatment with olanzapine, a serotonin receptor antagonist, has not been fully understood. Weight gain and food intake are under the control of neuropeptides/hormones, POMC (proopiomelanocortin), CART (cocaine and amphetamine regulated transcript), AgRP (Agouti-related peptide) and NPY (neuropeptide Y) that are synthesized and secreted from the arcuate nucleus (ARC) of hypothalamus. In this study, the altereration of the ARC neuropeptide/hormone levels both in humans and ...
Effect of gemcitabine and retinoic acid loaded PAMAM dendrimer-coated magnetic nanoparticles on pancreatic cancer and stellate cell lines
Yalcin, Serap; Erkan, Mert; Unsoy, Gozde; Parsian, Maryam; Kleeff, Jorg; Gündüz, Ufuk (2014-07-01)
Gemcitabine is an anticancer drug used in the treatment of different cancer types, including pancreatic ductal adenocarcinoma. The maximum tolerated dose in humans is restricted by its side effects on healty cells. Furthermore, the fibrotic stroma produced by the pancreatic stellate cells prevents effective delivery of chemotherapeutic agents providing a safe-haven for the cancer cells. This becomes more of a problem considering the short half-life of this drug. Magnetic nanoparticle-based targeted drug del...
Improvement of solubility of celecoxib by inclusion in MCM-41 mesoporous silica: drug loading and release
Gunaydin, Sahika; Yılmaz, Ayşen (2015-01-01)
Celecoxib is a poorly water-soluble nonsteroidal anti-inflammatory drug. Here we report four ordered mesoporous silica MCM-41 supports with different particle size, pore volume, and surface properties to investigate their loading capacity with celecoxib and their release abilities. Spherical MCM-41 mesoporous supports less than 50 nm in diameter were prepared and to compare the effect of the template removal process on morphology of samples, acid extraction and calcination methods were used. Moreover, nearl...
Citation Formats
Ö. Durukan, M. Akkulak, E. Evin, Ş. Arslan, and O. Adalı, “Alteration of protein and gene expressions of Hexokinase II in PC3 cell lines by cisplatinmetformin combination treatment,” 2018, vol. 8, p. 352, Accessed: 00, 2021. [Online]. Available: https://febs.onlinelibrary.wiley.com/doi/10.1002/2211-5463.12453.