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Dual inhibitory potential of ganoderic acid A on GLUT1/3: computational and in vitro insights into targeting glucose metabolism in human lung cancer

文献类型：期刊论文

作者Bashir, Mona Alrasheed1,2,3; Abdalla, Mohnad4,5; Shao, Chang-Sheng1,2; Wang, Han1,2; Bondzie-Quaye, Precious1,2; Almahi, Waleed Abdelbagi6; Swallah, Mohammed Sharif1,2; Huang, Qing1,2
刊名RSC ADVANCES
出版日期2024-09-04
卷号14
DOI10.1039/d4ra04454a
通讯作者Huang, Qing(huangq@ipp.ac.cn)
英文摘要Human glucose transporters (GLUTs) facilitate the uptake of hexoses into cells. In cancer, the increased proliferation necessitates higher expression of GLUTs, with particular emphasis on GLUT1 and GLUT3. Thus, inhibiting GLUTs holds promise as an anticancer therapy by starving these cells of fuel. Ganoderic acid A (GAA), a triterpene found in Ganoderma lucidum, has anticancer and antidiabetic properties. Recent studies show that GAA reduces glucose uptake in cancer cells, which indicates that GAA may affect GLUT1/GLUT3 by inhibiting glucose uptake. Therefore, this study aimed to inspect whether GAA could target GLUT1/GLUT3 and play an inhibitory role in changing their endofacial and exofacial conformations. To this end, AlphaFold2 was employed to model the endofacial and exofacial conformations of GLUT3 and GLUT1, respectively. Molecular docking, molecular dynamics simulation, cell viability, cellular thermal shift assays (CETSA), glucose uptake, qPCR, and western blotting were harnessed. In comparison to the endofacial (cytochalasin B) and exofacial (phloretin) GLUT1/3 inhibitors, the computational findings unveiled GAA's capacity to bind and stabilize GLUT1/3 in their two conformational states, with a preference for binding the endofacial conformation. A low, non-cytotoxic dose of GAA thermally stabilized both transporters and inhibited glucose uptake in human lung cancer cells, similar to cytochalasin B and phloretin. In conclusion, this study has unearthed novel functionalities of GAA, suggesting its potential utility in cancer therapy by targeting glucose metabolism.
WOS关键词DRUG TARGET ; CELLS ; APOPTOSIS ; OVEREXPRESSION ; PROLIFERATION ; TRANSPORTERS ; DISCOVERY ; CARCINOMA ; IMPROVES ; DOCKING
资助项目National Natural Science Foundation of China[11635013] ; National Science Foundation of China ; Chinese government
WOS研究方向Chemistry
语种英语
WOS记录号WOS:001307818900001
出版者ROYAL SOC CHEMISTRY
资助机构National Natural Science Foundation of China ; National Science Foundation of China ; Chinese government
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/135179]  
专题中国科学院合肥物质科学研究院
通讯作者Huang, Qing
作者单位1.Chinese Acad Sci, Inst Intelligent Machines, Hefei Inst Phys Sci, CAS Key Lab High Magnet Field & Ion Beam Phys Biol, Hefei 230031, Peoples R China
2.Univ Sci & Technol China, Grad Sch, Sci Isl Branch, Hefei 230026, Peoples R China
3.Omdurman Islamic Univ, Fac Sci & Technol, Dept Biotechnol, POB 382, Omdurman, Sudan
4.Shandong Univ, Childrens Hosp, Pediat Res Inst, Jinan 250022, Shandong, Peoples R China
5.Shandong Prov Clin Res Ctr Childrens Hlth & Dis, Jinan 250022, Shandong, Peoples R China
6.Chinese Acad Sci, Inst Hlth & Med Technol, Hefei Inst Phys Sci, Hefei Inst Phys Sci, Hefei 230031, Peoples R China
推荐引用方式
GB/T 7714		 Bashir, Mona Alrasheed,Abdalla, Mohnad,Shao, Chang-Sheng,et al. Dual inhibitory potential of ganoderic acid A on GLUT1/3: computational and in vitro insights into targeting glucose metabolism in human lung cancer[J]. RSC ADVANCES,2024,14.
APA Bashir, Mona Alrasheed.,Abdalla, Mohnad.,Shao, Chang-Sheng.,Wang, Han.,Bondzie-Quaye, Precious.,...&Huang, Qing.(2024).Dual inhibitory potential of ganoderic acid A on GLUT1/3: computational and in vitro insights into targeting glucose metabolism in human lung cancer.RSC ADVANCES,14.
MLA Bashir, Mona Alrasheed,et al."Dual inhibitory potential of ganoderic acid A on GLUT1/3: computational and in vitro insights into targeting glucose metabolism in human lung cancer".RSC ADVANCES 14(2024).

入库方式： OAI收割

来源：合肥物质科学研究院

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