(3R)‑5,6,7‑trihydroxy‑3‑isopropyl‑3‑methylisochroman‑1‑one inhibited osteosarcoma growth by inducing apoptosis

Song,Ming‑Zhu; Zhang,Feng‑Lin; Lin,Le‑Jun

doi:10.3892/etm.2019.7681

(3R)‑5,6,7‑trihydroxy‑3‑isopropyl‑3‑methylisochroman‑1‑one inhibited osteosarcoma growth by inducing apoptosis

Authors:
- Ming‑Zhu Song
- Feng‑Lin Zhang
- Le‑Jun Lin
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Affiliations: Department of Orthopaedics and Traumatology, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China, Department of Emergency, Yantai Hospital of Traditional Chinese Medicine, The Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical College, Yantai, Shandong 264000, P.R. China, Department of Nuclear Medicine, The Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical College, Yantai, Shandong 264000, P.R. China
Published online on: June 18, 2019 https://doi.org/10.3892/etm.2019.7681
Pages: 1107-1114
Copyright: © Song et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

As one of the leading causes of cancer‑associated mortalities worldwide, the overall survival rate of osteosarcoma has stably remained at 15‑30% for several decades. (3R)‑5,6,7‑trihydroxy‑3‑isopropyl‑3‑methylisochroman‑1‑one (TIM), isolated from the whole plant of Selaginella moellendorffii Hieron., has been reported to have pharmacological activities. In the present study, the anti‑proliferative effects of TIM against osteosarcoma were evaluated, and the underlying molecular mechanisms were explored. The results demonstrated that TIM inhibited proliferation and induced apoptosis in U2OS cells. Furthermore, the expression of the pro‑apoptotic protein NOXA in the intrinsic apoptosis pathway was upregulated by TIM, while the expression of myeloid cell leukemia 1, an anti‑apoptotic protein, was downregulated. In addition, TIM increased the protein expression of the endoplasmic reticulum stress markers inositol‑requiring enzyme 1, activating transcription factor 6 and glucose‑regulated protein 78. These results suggested that TIM induced ER stress response while activating intrinsic apoptosis. Furthermore, treating osteosarcoma tumor‑bearing mice with TIM significantly inhibited the tumor growth in the xenograft animal model. Overall, the study results suggested that TIM may serve as a potential antitumor agent against osteosarcoma.

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