Activation of PI3K/Akt/IKK-α/NF-κB signaling pathway is required for the apoptosis-evasion in human salivary adenoid cystic carcinoma: its inhibition by quercetin

Abstract

Quercetin, one of the most common natural flavonoids, has been reported to possess significant anti-tumor activities both in vitro and in vivo. The present study was to investigate the effects of quercetin on growth and apoptosis in human salivary adenoid cystic carcinoma (ACC). The result from MTT assay showed that quercetin decreased cell viability of both low metastatic cell line ACC-2 and high metastatic cell line ACC-M in a concentration- and time-dependent manner. Moreover, treatment with quercetin resulted in significantly increased apoptosis in ACC cells. Our data also revealed that the apoptosis induced by quercetin treatment was through a mitochondria-dependent pathway which showed close correlation with the down-regulation of the PI3K/Akt/IKK-alpha/NF-kappaB pathway. Most importantly, quercetin significantly prevented in vivo growth of ACC xenografts in nude mice, accompanied by induction of tumor cell apoptosis, suppression of NF-kappaB nuclear translocation, as well as down-regulation of Akt and IKK-alpha activation. In addition, we explored the clinical significance of the PI3K/Akt/IKK-alpha/NF-kappaB signaling axis in ACC by immunohistochemical analysis of tissue specimens followed by the clustering analyses. We determined that the PI3K/Akt/IKK-alpha/NF-kappaB pathway is ubiquitously activated in ACC and plays an essential role in the evasion of apoptosis. Taken together, the results from our study implicated that quercetin would be a promising chemotherapeutic agent against ACC through its function of down-regulating the PI3K/Akt/IKK-alpha/NF-kappaB signaling pathway.

Quercetin induces protective autophagy in gastric cancer cells: Involvement of Akt-mTOR- and hypoxia-induced factor 1α-mediated signaling

“…13,44,45 In the biological role of autophagy in quercetin-mediated apoptotic cell death, the autophagy inhibitor chloroquine was utilized to disrupt lysosomal function and prevent completion of autophagy. To this end, cells were treated with chloroquine, quercetin alone or in combination.…”

The effects of marsupialization on bone regeneration adjacent to keratocystic odontogenic tumors, and the mechanisms involved

“…All of the tumor sections were reviewed in a blinded manner by two pathologists. Immunohistochemical analyses were then conducted in accordance with our previous procedures (17,18). The staining intensities for the tested markers in the KCOT capsule wall adjacent to bone were estimatedsemiquantitatively as follows: -, no staining; +, mild; ++, moderate; or +++, intense.…”

“…Isolation of total RNA, synthesis of cDNA, and real-time qPCR were carried out in accordance with our previous description (17). GAPDH was selected as an internal control for each experiment.…”

Tetrandrine induces apoptosis by activating reactive oxygen species and repressing Akt activity in human hepatocellular carcinoma

“…26,27 Many studies have shown that some clinical chemotherapeutic agents could induce cancer cell apoptosis via regulating MAPKs and Akt kinase activity. [28][29][30] To determine the role of these kinases in tetrandrine-induced HCC apoptosis, Western blot analysis was used to evaluate the activity of MAPKs and Akt-related proteins after tetrandrine treatment.…”