img
Synergic Effects of Doxorubicin and Melatonin on Apoptosis and Mitochondrial Oxidative Stress in MCF 7 Breast Cancer Cells Involvement of TRPV1 Channels     
Yazarlar
Pınar Aslan Koşar
Süleyman Demirel Üniversitesi, Türkiye
Mustafa Nazıroğlu
Süleyman Demirel Üniversitesi, Türkiye
İshak Suat Övey
Doç. Dr. Bilal ÇİĞ Doç. Dr. Bilal ÇİĞ
Süleyman Demirel Üniversitesi, Türkiye
Özet
Transient receptor transient receptor potential vanilloid 1 (TRPV1) is a Ca2+-permeable channel gated by oxidative stress and capsaicin (CAP) and modulated by melatonin (MEL) and capsazepine (CPZ). A combination of doxorubicin (DOX) and MEL may offer a potential therapy for breast cancer by exerting antitumor and anti-apoptotic effects and modulating Ca2+ influx and TRPV1 activity. We aimed to investigate the effects of MEL and DOX on the oxidative toxicity of MCF-7 human breast cancer cells, in addition to the activity of the TRPV1 channel and apoptosis. The MCF-7 cells were divided into the following six treatment groups: control, incubated with MEL (0.3 mM), incubated with 0.5 mu M DOX, incubated with 1 mu M DOX, incubated with MEL + 0.5 mu M DOX, or incubated with MEL + 1 mu M DOX. The intracellular free Ca2+ concentration was higher in the DOX groups than in the control, and the concentration was decreased by MEL. The intracellular free Ca2+ concentration was further increased by treatment with the TRPV1 channel activator CAP (0.01 mM), and it was decreased by the CPZ (0.1 mM). The intracellular production of reactive oxygen species, mitochondrial membrane depolarization, apoptosis level, procaspase 9 and PARP activities, and caspase 3 and caspase 9 activities were higher in the DOX and MEL groups than in the control. Apoptosis and the activity of caspase 9 were further increased in the DOX plus MEL groups. Taken together, the findings indicate that MEL supported the effects of DOX by activation of TRPV1 and apoptosis, as well as by inducing MCF-7 cell death. As the apoptosis and caspase activity of cancer cells increase because of their elevated metabolism, MEL may be useful in supporting their apoptotic capacity.
Anahtar Kelimeler
Apoptosis | Breast cancer cells | Calcium signaling | Doxorubicin | Mitochondria | Oxidative stress
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı JOURNAL OF MEMBRANE BIOLOGY
Dergi ISSN 0022-2631
Dergi Tarandığı Indeksler SCI-Expanded
Makale Dili İngilizce
Basım Tarihi 04-2016
Cilt No 249
Sayı 1
Sayfalar 129 / 140
Doi Numarası 10.1007/s00232-015-9855-0
Makale Linki http://link.springer.com/10.1007/s00232-015-9855-0