15‑hydroxy‑6α,12‑epoxy‑7β,10αH,11βH‑spiroax‑4‑ene‑12‑one exerts anti‑tumor effects against osteosarcoma through apoptosis induction

An,Tian‑Zhi; Li,Zhi; Ni,Cai‑Fang; Zhou,Shi; Yang,Chao; Huang,Xue‑Qing; Li,Pei‑Cheng; Shen,Jian

doi:10.3892/etm.2020.8489

15‑hydroxy‑6α,12‑epoxy‑7β,10αH,11βH‑spiroax‑4‑ene‑12‑one exerts anti‑tumor effects against osteosarcoma through apoptosis induction

Authors:
- Tian‑Zhi An
- Zhi Li
- Cai‑Fang Ni
- Shi Zhou
- Chao Yang
- Xue‑Qing Huang
- Pei‑Cheng Li
- Jian Shen
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Affiliations: Department of Interventional Radiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550002, P.R. China
Published online on: February 4, 2020 https://doi.org/10.3892/etm.2020.8489
Pages: 2511-2518
Copyright: © An et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteosarcoma is the most common type of malignant bone tumor, which has an overall survival rate of only 15‑30%. The present study aimed to investigate the effects of 15‑hydroxy‑6α,12‑epoxy‑7β,10αH,11βH‑spiroax‑4‑ene‑12‑one (HESEO), a compound extracted from the endophytic fungus Penicillium sp. FJ‑1 isolated from Avicennia marina, on the proliferation of osteosarcoma cells and to explore its underlying mechanisms of action. Cell number was counted to measure the cell proliferation. JC‑1 reagent was used to measure mitochondrial membrane potential. ELISA was used to measure the cytochrome c level and caspase activities. Apoptosis was detected by Annexin V‑Propidium Iodide staining. Gene and protein expression were measured by reverse‑transcription‑PCR and western blot analysis, respectively. Additionally, the anti‑tumor effects of HESEO were explored within a syngeneic osteosarcoma tumor model. The results suggested that HESEO significantly inhibited the proliferation of osteosarcoma cells and induced apoptosis of MG‑63 cells, evidenced by their decreased mitochondrial membrane potential, and increased cytochrome c release, caspase activities and percentage of apoptotic cells. In addition, HESEO increased the expression of pro‑apoptotic genes and proteins compared with control cells. The results indicated that HESEO may act through increasing p53 upregulated modulator of apoptosis expression. Furthermore, HESEO treatment significantly increased the survival time and decreased the tumor burden of osteosarcoma tumor‑bearing mice compared with vehicle treatment. Furthermore, combined treatment with HESEO enhanced the effects of the chemotherapeutic agent methotrexate on a lung metastasis osteosarcoma model. These data suggested that HESEO could be developed as a potential anti‑tumor agent against osteosarcoma.

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