Capsaicin inhibits cell proliferation by enhancing oxidative stress and apoptosis through SIRT1/NOX4 signaling pathways in HepG2 and HL-7702 cells
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Dosyalar
Tarih
2022
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Wiley
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Capsaicin could suppress the proliferation of cancer cells and inhibit many biochemical pathways associated with tumorigenesis and metastasis. This study investigates the effects of capsaicin in both hepatocellular carcinoma (HepG2) and normal hepatocytes (HL-7702) via the SIRT1/NOX4 signaling pathway. After determination of cytotoxic concentrations of capsaicin on HL-7702 and HepG2 cells, we measured total oxidant status (TOS), reduced glutathione (GSH), 8-hydroxydeoxyguanosine (8-OHdG), cytochrome c (CYC), caspase3 (CASP3), Bcl-2, Bax, sirtuin1 (SIRT1), and NADPH oxidases4 (NOX4) levels. Besides this, we analyzed the messenger RNA and protein levels of SIRT1 and NOX4. We found that capsaicin increased TOS, 8-OHdG, CASP3, CYC, Bax, and NOX4 levels, and decreased Bcl-2, GSH, and SIRT1 in a concentration-dependent manner in HepG2 cells. However, especially low capsaicin concentration (128.75 mu M) enhanced GSH and SIRT levels and reduced TOS, CASP3, CYC, 8-OHdG, and NOX4 levels in HL-7702 cells (p < 0.05). Interestingly, 128.75 and 172.8 mu M capsaicin treatment increased SIRT1 expression levels in HL-7702 cells, resulting in an increase in GSH levels and a decrease in TOS, CYC, CAPS3, and 8-OHdG levels through NOX4 inhibition. Furthermore, we demonstrated a significant decrease in SIRT1 protein levels and an increase in NOX4 protein levels and caspase-3/-7 activities in both HL-7702 and HepG2 cells treated with 261.5 mu M capsaicin. Additionally, morphological changes in HL-7702 and HepG2 cells treated with capsaicin correlated with the enhancement in oxidative burden, DNA damage, and apoptosis. Our results show that capsaicin effectively might cause higher oxidative, apoptotic, and DNA damage in HepG2 cells than in HL-7702 cells through the SIRT1/NOX4 signaling pathway.
Açıklama
Anahtar Kelimeler
Apoptosis; Capsaicin; Dna Damage Sirt1; Hepg2; Hl-7702; Nox4; Oxidative Stress, Nadph Oxidases; Anticancer Properties; Cancer Cells; Nox Family; In-Vitro; Generation; Induction; Roles; Death
Kaynak
Journal of Biochemical and Molecular Toxicology
WoS Q Değeri
Q2
Scopus Q Değeri
Q2
Cilt
36
Sayı
3
