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. 2017 Oct;14(4):3067-3073.
doi: 10.3892/etm.2017.4855. Epub 2017 Jul 31.

Cordycepin induces apoptosis of human acute monocytic leukemia cells via downregulation of the ERK/Akt signaling pathway

Yue Wang  1 , Huimin Mo  2   3 , Jun Gu  1 , Kan Chen  1 , Zhihua Han  1 , Yi Liu  4
Affiliations

Cordycepin induces apoptosis of human acute monocytic leukemia cells via downregulation of the ERK/Akt signaling pathway

Yue Wang et al. Exp Ther Med. 2017 Oct.

Abstract

The aim of the present study was to examine the apoptotic effect of cordycepin (COR) on human THP-1 acute monocytic leukemia cells. THP-1 cells were exposed to different concentrations of COR for 24, 48, 72 or 96 h. The cell viability and apoptotic rate were analyzed. The gene expression of Akt1, Akt2, Akt3, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were assessed by reverse-transcription quantitative PCR. Western blot analysis was used to detect the protein levels of phosphorylated (p)-Akt, p-extracellular signal-regulated kinase (ERK) and cleaved caspase-3. It was found that the viability of THP-1 cells was inhibited by COR in a dose- and time-dependent manner. After treatment with 200 µM COR for 24 h, the percentage of apoptotic cells was significantly increased. COR also downregulated the levels of Bcl-2, Akt1, Akt2 and Akt3, and elevated the expression of Bax. The protein levels of p-Akt and p-ERK were suppressed and cleaved caspase-3 was increased after treatment of COR. In conclusion, COR was found to induce apoptosis of THP-1 acute monocytic leukemia cells through downregulation of ERK/Akt signaling.

Keywords: Akt; ERK; THP-1; apoptosis; caspase-3; cordycepin.

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Figures

Figure 1.
Figure 1.
Anti-proliferative effects of COR on THP-1 cells. (A-D) A Cell Counting Kit-8 assay demonstrated the anti-proliferative effects of COR on THP-1 cells after treatment for 24, 48, 72 and 96 h. Values are expressed as the mean ± standard error. *P<0.05; **P<0.01; ***P<0.001 vs. untreated group. COR, cordycepin.
Figure 2.
Figure 2.
Apoptosis of THP-1 cells following COR treatment. (A-F) Flow cytometry-based assessment of apoptosis in THP-1 cells following treatment with 0, 25, 50, 100, 150, 200 µM of COR. Annexin V-fluorescein isothiocyanate is displayed on the x-axis. (G-I) Quantitative analysis of total, early and late apoptotic rate. Values are expressed as the mean ± standard error. *P<0.05; **P<0.01; ***P<0.001 vs. untreated group. COR, cordycepin; PI, propidium iodide.
Figure 3.
Figure 3.
Apoptosis-associated gene expression in THP-1 cells after COR treatment. Reverse-transcription quantitative polymerase chain reaction analysis was employed to detect the expression of (A) Bcl-2 and (B) Bax in COR-treated THP-1 cells. Values are expressed as the mean ± standard error. **P<0.01; ***P<0.001 vs. untreated group. COR, cordycepin; Bcl-2, B-cell lymphoma 2; Bax, Bcl-2-associated X protein.
Figure 4.
Figure 4.
Cell survival-associated gene expression in THP-1 cells after COR treatment. Reverse-transcription quantitative polymerase chain reaction analysis was employed to detect the expression of (A) Akt1, (B) Akt2 and (C) Akt3 in COR-treated THP-1 cells. Values are expressed as the mean ± standard error. *P<0.05; **P<0.01; ***P<0.001 vs. untreated group. COR, cordycepin.
Figure 5.
Figure 5.
Western blot analysis of p/total-Akt, p-ERK/total-ERK and cleaved caspase-3 levels following apoptosis induction by COR in THP-1 cells. (A-C) Representative western blot displaying the levels of (A) p/total-Akt, (B) quantified, (C) p-ERK/total-ERK, (D) quantifies, (E) cleaved caspase-3 and, (F) quantified in THP-1 cells following COR treatment. Values were normalized to β-actin. Values are expressed as the mean ± standard error. *P<0.05; **P<0.01; ***P<0.001 vs. untreated group. COR, cordycepin; p-ERK, phosphorylated extracellular signal-regulated kinase.
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