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Anti-osteosarcoma activity and underlying molecular mechanism of a novel small molecule spermine oxidase inhibitor SI-4650
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You ZHOU, Yan-lin WANG, Li-dan SUN, Chun-yu CAO, Jian-lin YANG*
Acta Pharmaceutica Sinica | 2019, 54(3) : 454 - 462
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Acta Pharmaceutica Sinica | 2019, 54(3): 454-462
• Original Articles •
Anti-osteosarcoma activity and underlying molecular mechanism of a novel small molecule spermine oxidase inhibitor SI-4650
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You ZHOU, Yan-lin WANG, Li-dan SUN, Chun-yu CAO, Jian-lin YANG*
Affiliations
  • Medical College of China Three Gorges University, Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, Yichang 443002, China
Published: 2019-03-12 doi: 10.16438/j.0513-4870.2018-1055
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The purpose of this study is to further explore the effects of SI-4650, a newly discovered small molecule inhibitor of spermine oxidase (SMO) in our laboratory, on proliferation and migration of human osteosarcoma 143B cells and its underlying molecular mechanism. Chemiluminescence and high performance liquid chromatograph were used to analyze the effect of SI-4650 on SMO activity in 143B cells. DCFH-DA-staining/FCM was used to analyze the accumulation of cellular reactive oxygen species (ROS), whereas MTT and FCM were used to detect proliferation and cell cycle. Transwell culture and Western blot were used to analyze the expression levels of migration-related proteins. PI/FITC-Annexin V/FCM, fluorescence microscopy and Western blot were used to analyze apoptosis and autophagy. Our results showed that SI-4650 could significantly decrease SMO activity, inhibit cell proliferation or migration, and induce a S-phase cell cycle arrest in 143B human osteosarcoma cells. The mechanism may be related to interfering with polyamine metabolism, activating mitochondrial-mediated apoptosis and causing autophagic death. These results suggest that SI-4650 has the potential for clinical use in treatment of osteosarcoma.

polyamine metabolism  /  spermine oxidase inhibitor  /  human osteosarcoma cell  /  cell proliferation  /  migration  /  apoptosis  /  autophagy
You ZHOU, Yan-lin WANG, Li-dan SUN, Chun-yu CAO, Jian-lin YANG. Anti-osteosarcoma activity and underlying molecular mechanism of a novel small molecule spermine oxidase inhibitor SI-4650[J]. Acta Pharmaceutica Sinica, 2019 , 54 (3) : 454 -462 . DOI: 10.16438/j.0513-4870.2018-1055
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Article Info
doi: 10.16438/j.0513-4870.2018-1055
  • Receive Date：2018-11-22
  • Online Date：2026-01-26
  • Published：2019-03-12
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  • Received：2018-11-22
  • Revised：2018-12-28
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    Medical College of China Three Gorges University, Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, Yichang 443002, China
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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