Combination of HDE and BIIB021 efficiently inhibits cell proliferation and induces apoptosis via downregulating hTERT in myelodysplastic syndromes

Wang,Bo; Jiang,Jianping; Zhang,Yun; Shen,Yingying; Wu,Liqiang; Tang,Siqi; Lin,Shengyun

doi:10.3892/etm.2021.9934

Combination of HDE and BIIB021 efficiently inhibits cell proliferation and induces apoptosis via downregulating hTERT in myelodysplastic syndromes

Authors:
- Bo Wang
- Jianping Jiang
- Yun Zhang
- Yingying Shen
- Liqiang Wu
- Siqi Tang
- Shengyun Lin
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Affiliations: Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China, Preparation Center, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China, Laboratory of Molecular Neuropharmacology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, P.R. China
Published online on: March 17, 2021 https://doi.org/10.3892/etm.2021.9934
Article Number: 503

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Abstract

Treatment for higher‑risk patients with myelodysplastic syndrome (MDS) should aim to modify the disease course by avoiding progression to acute myeloid leukemia and improving survival. When a patient is not eligible for intensive chemotherapy and lacks a donor hematopoietic cell source, or for a patient in a poor economic situation, consideration can be given to the use of Chinese herbal medicine. Numerous plant extracts, such as camptothecin, vinblastine and paclitaxel, have been reported to display antitumor effects, serving as potential therapeutic strategies for cancer. In the present study, the ultra‑performance liquid chromatography‑tandem mass spectrometry system (Waters Corporation) was used to detect the main chemical components of HDE, CCK‑8 assay to detect the effects of HDE and BIIB021 on the proliferation of SKM‑1 cells; and designed hTERT‑small interfering (si)RNAs to detect the effects of HDE and BIIB021 on SKM‑1 cell apoptosis after HTERT gene knockdown. The present study investigated a newly extracted coumarin HDE, the active component in Oldenlandia diffusa Willd, which efficiently inhibited SKM‑1 (MDS cell line) proliferation and induced apoptosis, as determined by performing Cell Counting Kit‑8 and flow cytometry assays, respectively. The effect of HDE was associated with decreased telomerase activity. Moreover, heat shock protein 90 inhibitor BIIB021 significantly enhanced the antitumor effects of HDE on SKM‑1 cells. In addition, SKM‑1 cell apoptosis was increased in human telomerase reverse transcriptase (hTERT)‑knockdown cells compared with the negative control group. Cell apoptosis in hTERT‑knockdown SKM‑1 cells was further enhanced following HDE, BIIB021 or combination treatment, as evidenced by increased levels of cleaved caspase 3, cleaved caspase 8 and cleaved poly ADP ribose polymerase. Collectively, the results indicated synergistic antitumor effects of HDE and BIIB021, providing a novel therapeutic combination for higher‑risk MDS.

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