Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.11851/8738
Title: Effects of Melatonin and Doxorubicin on Primary Tumor And Metastasis in Breast Cancer Model
Authors: Tanriover G.
Dilmac S.
Aytaç, Güneş
Farooqi A.A.
Sindel M.
Keywords: angiogenesis
Breast cancer
doxorubicin
MDSC
melatonin
metastasis
doxorubicin
melatonin
animal
brain tumor
breast tumor
female
human
metabolism
metastasis
mouse
myeloid-derived suppressor cell
pathology
tumor cell line
Animals
Brain Neoplasms
Breast Neoplasms
Cell Line, Tumor
Doxorubicin
Female
Humans
Melatonin
Mice
Myeloid-Derived Suppressor Cells
Neoplasm Metastasis
Issue Date: 2022
Publisher: Bentham Science Publishers
Source: Tanriover, G., Dilmac, S., Aytac, G., Farooqi, A. A., & Sindel, M. (2022). Effects of melatonin and doxorubicin on primary tumor and metastasis in breast cancer model. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 22(10), 1970-1983.
Abstract: Background: Melatonin exerts oncostatic effects on breast cancer via immunomodulation and anti-oxidation. Doxorubicin is an effective chemotherapeutic agent, but parallel studies also provide ample evidence of an off-target effect of Doxorubicin in breast cancer patients. Objective: Combinatorial use of doxorubicin and melatonin has not been comprehensively analyzed in breast cancer models. We hypothesized that the anti-oxidative, anti-proliferative and anti-inflammatory effects of melatonin could ameliorate the off-target effects of doxorubicin in breast cancer patients and enhance the anti-tumoral effects of doxo-rubicin. The goal of the study is to test this hypothesis in cancer cell lines and xenografted mice. Methods: The effects of Melatonin and doxorubicin on the cell viability were evaluated in 4T1-Brain Metastatic Tumor (4TBM). Furthermore, the effects of melatonin and doxorubicin on the primary tumors and systemic metastasis were evaluated in the xenografted mice. Lung and liver tissues were removed and metastasis analyses were performed. The levels of p65, phospho-STAT3, CD11b+, GR1+, Ki67, and cleaved caspase-3 proteins were determined with im-munohistochemistry and western blot analysis. We examined the effects of melatonin and Melatonin+Doxorubicin combination therapy on 4TBM cells. Results: Our results showed that doxorubicin inhibited the proliferation of metastatic breast cancer cells while melato-nin did not affect cells. Tumor growth and metastasis were markedly suppressed in melatonin alone and in combination with doxorubicin. The expression of CD11b+ and GR1+ proteins, which are indicators of myeloid-derived suppressor cells (MDSCs), were noted to be reduced in both primary tumor and metastatic tissues in melatonin and doxorubicin groups. Conclusion: The combination of melatonin with doxorubicin reduced primary tumor growth and distant metastasis. Based on these results, melatonin is a promising candidate for combinatory use with conventional chemotherapeutics for breast cancer treatment. © 2022 Bentham Science Publishers.
URI: https://doi.org/10.2174/1871520621666211213094258
https://hdl.handle.net/20.500.11851/8738
ISSN: 1871-5206
Appears in Collections:PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Temel Tıp Bilimleri Bölümü / Department of Basic Medical Sciences
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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