Capsaicin Reduces Cancer Stemness and Inhibits Metastasis by Downregulating <i>SOX2</i> and <i>EZH2</i> in Osteosarcoma

作者全名："Chen, Zhi-Yu; Huang, Huan-Huan; Li, Qiao-Chu; Zhan, Fang-Biao; Wang, Ling-Bang; He, Tao; Yang, Chao-Hua; Wang, Yang; Zhang, Yuan; Quan, Zheng-Xue"

作者地址："[Chen, Zhi-Yu; Li, Qiao-Chu; Wang, Ling-Bang; He, Tao; Yang, Chao-Hua; Wang, Yang; Quan, Zheng-Xue] Chongqing Med Univ, Orthoped Lab, Chongqing 40016, Peoples R China; [Chen, Zhi-Yu; Li, Qiao-Chu; Wang, Ling-Bang; He, Tao; Yang, Chao-Hua; Wang, Yang; Quan, Zheng-Xue] Chongqing Med Univ, Dept Orthoped, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Huang, Huan-Huan] Chongqing Med Univ, Affiliated Hosp 1, Dept Nursing, Chongqing 400016, Peoples R China; [Zhan, Fang-Biao] Chongqing Univ, Dept Orthoped, Gorges Hosp Wanzhou 3, Chongqing 404000, Peoples R China; [Zhang, Yuan] Chongqing Med Univ, Dept Orthopaed, Chongqing 400014, Peoples R China; [Zhang, Yuan] Chongqing Med Univ, Key Lab Child Childrens Hosp, Minist Educ, Chongqing 400014, Peoples R China; [Quan, Zheng-Xue] Chongqing Med Univ, Dept Orthopaed, Childrens Hosp, Chongqing 400014, Peoples R China"

通信作者："Quan, ZX (通讯作者)，Chongqing Med Univ, Orthoped Lab, Chongqing 40016, Peoples R China.; Quan, ZX (通讯作者)，Chongqing Med Univ, Dept Orthoped, Affiliated Hosp 1, Chongqing 400016, Peoples R China.; Zhang, Y (通讯作者)，Chongqing Med Univ, Dept Orthopaed, Chongqing 400014, Peoples R China.; Zhang, Y (通讯作者)，Chongqing Med Univ, Key Lab Child Childrens Hosp, Minist Educ, Chongqing 400014, Peoples R China.; Quan, ZX (通讯作者)，Chongqing Med Univ, Dept Orthopaed, Childrens Hosp, Chongqing 400014, Peoples R China."

来源：AMERICAN JOURNAL OF CHINESE MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000980634300002

JCR分区：Q1

影响因子：5.7

年份：2023

卷号：51

期号：4

开始页：1041

结束页：1066

文献类型：Article

关键词：Capsaicin; Osteosarcoma; Cancer Stem Cells; Metastasis; mRNAsi

摘要："Metastasis of osteosarcoma is an important adverse factor affecting patients' survival, and cancer stemness is the crucial cause of distant metastasis. Capsaicin, the main component of pepper, has been proven in our previous work to inhibit osteosarcoma proliferation and enhance its drug sensitivity to cisplatin at low concentrations. This study aims to further explore the anti-osteosarcoma effect of capsaicin at low concentrations (100 mu M, 24 h) on stemness and metastasis. The stemness of human osteosarcoma (HOS) cells was decreased significantly by capsaicin treatment. Additionally, the capsaicin treatment's inhibition of cancer stem cells (CSCs) was dose-dependent on both sphere formation and sphere size. Meanwhile, capsaicin inhibited invasion and migration, which might be associated with 25 metastasis-related genes. SOX2 and EZH2 were the most two relevant stemness factors for capsaicin's dose-dependent inhibition of osteosarcoma. The mRNAsi score of HOS stemness inhibited by capsaicin was strongly correlated with most metastasis-related genes of osteosarcoma. Capsaicin downregulated six metastasis-promoting genes and up-regulated three metastasis-inhibiting genes, which significantly affected the overall survival and/or diseasefree survival of patients. In addition, the CSC re-adhesion scratch assay demonstrated that capsaicin inhibited the migration ability of osteosarcoma by inhibiting its stemness. Overall, capsaicin exerts a significant inhibitory effect on the stemness expression and metastatic ability of osteosarcoma. Moreover, it can inhibit the migratory ability of osteosarcoma by suppressing its stemness via downregulating SOX2 and EZH2. Therefore, capsaicin is expected to be a potential drug against osteosarcoma metastasis due to its ability to inhibit cancer stemness."

基金机构："National Natural Science Foundation of China [82072976]; General project of Chongqing Natural Science Foundation [cstc2019jcyj-msxmX0853, cstc2021jcyj-msxm1127]; General Basic Research Project from Ministry of Education KeyLaboratory of Child Development and Disorders [GBRP-202117]; Innovative Project for doctoral students in the First Affiliated Hospital of Chongqing Medical University [CYYY-RSY ISCXXM-202214]"

基金资助正文："We thank Dr. Huifeng Pi (Third Military Medical University) for generously sharing hisknowledge of biology and guiding experiments. And, we also thank Dr. Shipeng Guo(Chongqing Medical University) for his guidance on R and for sharing his experience. Thiswork was supported by the National Natural Science Foundation of China [82072976], the General project of Chongqing Natural Science Foundation [cstc2019jcyj-msxmX0853,cstc2021jcyj-msxm1127], General Basic Research Project from Ministry of Education KeyLaboratory of Child Development and Disorders (No. GBRP-202117) and the InnovativeProject for doctoral students in the First Affiliated Hospital of Chongqing MedicalUniversity (CYYY-RSY ISCXXM-202214)"