Adenosine induces intrinsic apoptosis via the PI3K/Akt/mTOR signaling pathway in human pharyngeal squamous carcinoma FaDu cells Corrigendum in /10.3892/ol.2019.10014

Choi,Mi  Suk; Moon,Sung‑Min; Lee,Seul  Ah; Park,Bo‑Ram; Kim,Jae‑Sung; Kim,Do   Kyung; Kim,Yong  Hwan; Kim,Chun  Sung

doi:10.3892/ol.2018.8089

Adenosine induces intrinsic apoptosis via the PI3K/Akt/mTOR signaling pathway in human pharyngeal squamous carcinoma FaDu cells

Corrigendum in: /10.3892/ol.2019.10014

Authors:
- Mi Suk Choi
- Sung‑Min Moon
- Seul Ah Lee
- Bo‑Ram Park
- Jae‑Sung Kim
- Do Kyung Kim
- Yong Hwan Kim
- Chun Sung Kim
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Affiliations: Department of Dental Hygiene, Chodang University, Muan‑ro, Muan‑eup, Muan 534‑701, Republic of Korea, CStech Research Institute, Gwangju, South Jeolla 61007, Republic of Korea, Department of Oral Biochemistry, College of Dentistry, Chosun University, Gwangju, South Jeolla 501‑759, Republic of Korea, Pre‑Dentistry, College of Dentistry, Chosun University, Gwangju, South Jeolla 501‑759, Republic of Korea, Department of Oral Physiology, College of Dentistry, Chosun University, Gwangju, South Jeolla 501‑759, Republic of Korea, Department of Crop Science and Biotechnology, College of Life and Resource Science, Cheonan, Chungnam 31116, Republic of Korea
Published online on: February 20, 2018 https://doi.org/10.3892/ol.2018.8089
Pages: 6489-6496

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Abstract

Adenosine has been identified to occur abundantly intra-and extracellularly, and to exert diverse biological functions, including the suppression of cell proliferation and the induction of apoptosis. Adenosine has been reported to induce apoptosis in several cancer cell lines; however, to the best of our knowledge, the effect of adenosine on head and neck cancer cells has not been investigated. Therefore, the purpose of the present study was to evaluate whether adenosine exerts any anticancer effect via induction of apoptosis in human pharyngeal squamous carcinoma FaDu cells. An MTT assay demonstrated that adenosine‑treated FaDu cells inhibited a dose‑dependent rate of cell growth, whereas human oral keratinocytes cells were unaffected by adenosine treatment. In addition, A1 and A2a adenosine receptor mRNA was detected in FaDu cells by reverse transcription‑polymerase chain reaction, and adenosine‑induced FaDu cell death was significantly suppressed by treatment with ATL‑444, an antagonist of these receptors. Furthermore, adenosine‑induced cell growth inhibition was exerted via apoptosis, as confirmed by the analysis of DNA fragmentation, Hoechst nuclear staining and flow cytometry with Annexin V‑fluorescein isothiocyanate and propidium iodide staining. Adenosine was also demonstrated to induce an increase in Bcl‑associated X expression, a decrease in B‑cell lymphoma 2 expression, the release of cytochrome c from mitochondria, and the activation of caspase‑3, ‑9 and poly(ADP‑ribose) polymerase in FaDu cells. Finally, phosphoinositide 3‑kinase (PI3K), RAC serine/threonine‑protein kinase (Akt) and mechanistic target of rapamycin (mTOR) phosphorylation was found to be significantly inhibited in adenosine‑treated FaDu cells, as was phosphorylation of the mTOR downregulators, S6 kinase β1, eukaryotic translation initiation factor 4E‑binding protein 1, and eukaryotic translation initiation factor 4 γ1. Taken together, these results indicate that adenosine induces apoptosis via the mitochondrial intrinsic pathway, and activates caspase-3 and -9 activity via the PI3K/Akt/mTOR signaling pathway.

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