Tag Archives: topotecan
Effect of IRAK1/4 inhibitor on IL-1β, IL-6, INF-γ and TNF-α expression in breast cancer cells of several lines
M. Rezaei1, B. Shahouzehi2,4, S. Rahemi1,3, H. Fallah1*, M. Salarkarimi1
1Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran;
2Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran;
3Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran;
4Student Research Committee, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran;
*e-mail: hf59ma@gmail.com
Received: 28 July 2020; Accepted: 07 July 2021
Recent studies have shown that inflammation mediated via interleukin-1 receptor-associated kinases (IRAKs) is associated with cancer cells drug resistance. We aimed to evaluate the expression of inflammatory cytokines as the potential mechanism involved in the development of cancer cells resistance to conventional chemotherapy drugs. Breast cancer cells of BT549, BT20 and MB468 lines were treated with IRAK 1/4 inhibitor alone or in combination with chemotherapeutic agents methotrexate and topotecan. Expression of IL-1β, IL-6, TNF-α, and IFN-γ genes was quantified by real-time PCR. It was found that IRAK1/4 inhibitor suppressed IL-1β expression in BT549 cells at most and had minimal effect on IL-6 expression in MB468 cells. For the first time we showed that concomitant use of IRAK1/4 inhibitor with topotecan and methotrexate reduced IL-1β, IFN γ, TNF-α and IL-6 expression in BT-20, BT-549, MB-468 cell lines compared to the controls. It is suggested that specific IRAK inhibitors in combination with conventional chemotherapy can be used in cancer treatment to increase drug sensitivity and decrease the risk of tumor recurrence.
Studies by means of (1)H NMR spectroscopy of complex formation of aromatic biologically active compounds with antibiotic topotecan
A. A. Mosunov, V. V. Kostjukov, M. P. Evstigneev
Sevastopol National Technical University, Ukraine;
e-mail: max_evstigneev@mail.ru
The analysis of heteroassociation of antibiotic topotecan (TPT) with aromatic biologically active compounds (BAC): caffeine, mutagens ethidium bromide and proflavine, antibiotic daunomycin, vitamins flavin-mononucleotide and nicotinamide, has been carried out in the work using 1H NMR spectroscopy data. The equilibrium constants of heteroassociation and induced chemical shifts of the protons have been obtained in the complexes with BAC. It is found that the complex formation TPT-BAC has the nature of stacking of the chromophores, additionally stabilized in the case of proflavine by intermolecular hydrogen bond. Calculation of the basic components of the Gibbs free energy of the complexation reactions is carried out, and the factors which stabilize and destabilize the heterocomplexes of molecules are revealed.