7,8-Dihydroxycoumarin inhibits A549 human lung adenocarcinoma cell proliferation by inducing apoptosis via suppression of Akt/NF-κB signaling

Abstract

The Akt/NF-κB pathways are involved in numerous anti-apoptotic and drug-resistance events that occur in non-small cell lung cancer (NSCLC). In the present study, the role of 7,8-dihydroxycoumarin in the regulation of the anti-apoptotic Akt and NF-κBp65 signaling pathways was explored. A549 human lung adenocarcinoma cells were exposed to 7,8-dihydroxycoumarin with a final concentration of 25, 50 and 100 μmol/l for 48 h. Quantitative polymerase chain reaction (PCR) and western blotting were performed to detect mRNA and protein expression, respectively. The MTT assay was performed to detect cell proliferation. The results demonstrated that anti-apoptotic phospho-Akt1 (pAkt1), phospho-IκBα (pIκBα), NF-κBp65 and Bcl-2 were inhibited and pro-apoptotic caspase-3 was upregulated in a concentration-dependent manner. At a concentration of 100 μmol/l, the anti-apoptotic NF-κBp65 and Bcl-2 mRNA expression levels decreased 0.12 (5.82/48.5, treated/control)-fold and 0.17 (6.7/39.4, treated/control)-fold, respectively. The pro-apoptotic caspase-3 mRNA was upregulated 4.43 (39.4/8.9, treated/control)-fold. The anti-apoptotic pAkt1, pIκBα, NF-κBp65 and Bcl-2 proteins were downregulated, with blot grayscale values of 7.3 (vs. 52.4 control), 4.3 (vs. 42.2 control), 5.08 (vs. 44.5 control) and 5.92 (vs. 38.5 control), respectively. The proapoptotic caspase-3 was upregulated to a blot grayscale value of 27.8 (vs. 5.8 control). The proliferative activity of A549 cells was reduced significantly compared with that of the control cells (83.7, 27.2 and 9.5 vs. 100%, respectively; P<0.05 for each). 7,8-Dihydroxycoumarin plays an important role in the induction of apoptosis via suppression of Akt/NF-κB signaling in A549 human lung adenocarcinoma cells in a concentration-dependent manner. 7,8-Dihydroxycoumarin may be a candidate naturally-occurring drug for the treatment and prevention of lung adenocarcinoma.

Daphnetin inhibits proliferation and inflammatory response in human HaCaT keratinocytes and ameliorates imiquimod-induced psoriasis-like skin lesion in mice

“…Several compounds have been found to exhibit attractive therapeutic potential for psoriasis though inhibiting NF-κB signaling pathway [10,[40][41][42][43]. Daphnetin was reported to inhibit proliferation and inflammation by regulating the NF-κB signaling pathway [13,16,17]. In order to investigate whether daphnetin-mediated inhibition of proliferation and inflammatory response in HaCaT keratinocytes is resulted from NF-κB signaling inactivation, p65 phosphorylation and p65 nuclear translocation were detected.…”

“…Daphnetin (7,, a natural coumarin compound isolated from Daphne odora var., exhibits broad bioactivities including anti-proliferation and anti-inflammation [11,12]. Daphnetin was found to inhibit A549 human lung adenocarcinoma cell proliferation by inducing apoptosis via suppression of Akt/NF-κB signaling [13]. Daphnetin ameliorates 7,12-dimethylbenz [a] anthracene-induced mammary carcinogenesis through dual inhibition on Nrf-2-Keap1 and NF-κB pathways [14].…”

Daphnetin protects oxidative stress-induced neuronal apoptosis via regulation of MAPK signaling and HSP70 expression

“…Currently, great effort is being made to identify potent natural antioxidants with neuroprotective potential, due to their low toxicity and absence of clear side effects. Daphnetin, a natural antioxidant, exhibits a variety of biological effects, including anti-inflammatory and antitumor effects (14). Recently, studies have demonstrated that daphnetin exhibits a neurotrophic effect on peripheral nerve regeneration by suppressing nuclear factor-κB expression (15), provides a neuroprotective effect against glutamate-induced toxicity in immortalized mouse hippocampal HT22 cells and ischemic brain injury (16), and prevents excitotoxicity by inhibiting the N-methyl D-aspartate receptor subtype 2B -containing receptors and the subsequent calcium overload in cultured cortical neurons (17).…”

Cytokine-induced killer cells induce apoptosis and inhibit the Akt/nuclear factor-κB signaling pathway in cisplatin-resistant human glioma U87MG cells

“…The NF-κB/AKT signaling pathway is involved in the MDR reversal of CIK. It has been reported that activation of NF-κB followed by Akt phosphorylation has a role in the regulation of cell survival, apoptosis and drug resistance (8,9). The present study therefore investigated whether the intracellular AKT/NF-κB signaling pathway was involved in the effects of CIK on MDR.…”