Background:Oral cancer remains a significant global health challenge,as it has high morbidity and mortality rates.Current treatments show limited efficacy and have severe side effects,prompting searches for new therap...Background:Oral cancer remains a significant global health challenge,as it has high morbidity and mortality rates.Current treatments show limited efficacy and have severe side effects,prompting searches for new therapeutic agents.SH003,a traditional herbal formulation comprising Astragalus membranaceus,Angelica gigas,and Trichosanthes kirilowii,has demonstrated potential anticancer properties in previous studies.However,its specific efficacy against oral cancer and the role of its key components,particularly Cucurbitacin D,remain underexplored.Methods:The cytotoxic effects of SH003 and its major components—i.e.,Cucurbitacin D,Decursin,Formononetin,and Nodakenin—were evaluated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide(MTT),Trypan Blue exclusion,and Lactate Dehydrogenase(LDH)release assays.Cell migration was analyzed via wound healing assays,and apoptosis induction was assessed using cell cycle analysis and caspase activation assays.Epithelial-tomesenchymal transition(EMT)marker expression(E-cadherin and N-cadherin)was measured using Western blotting and Quantitative reverse transcription PCR(qRT-PCR).Results:SH003 significantly reduced cell viability in a dosedependent manner,with YD-8 and YD-9 cells showing greater sensitivity than YD-38 cells.Of the individual compounds,Cucurbitacin D was identified as a key active agent,as it exhibited potent inhibition of cell migration and significant modulation of EMT markers,including the upregulation of E-cadherin and downregulation of N-cadherin.These effects were most pronounced in YD-9 cells.Conclusions:Taken together,these findings suggest that Cucurbitacin D plays a crucial role mediating the anticancer activity of SH003,particularly via the reversal of EMT and the reduction of migratory and invasive potential of oral cancer cells.This study provides valuable insight into the mechanistic basis of SH003,highlighting its potential as a therapeutic agent against oral cancer.Further research,including in vivo studies and clinical trials,is needed to elucidate its precise mechanisms and potential applications against other cancer types.展开更多
Objective:CLT-003 is a novel phenylphthalimide derivative encapsulated in poly(lactate-glycolic acid)copolymer nanoparticles using nanotechnology techniques.CLT-003 possesses anti-angiogenetic and antitumor activities...Objective:CLT-003 is a novel phenylphthalimide derivative encapsulated in poly(lactate-glycolic acid)copolymer nanoparticles using nanotechnology techniques.CLT-003 possesses anti-angiogenetic and antitumor activities.Nevertheless,the role and molecular mechanism underlying CLT-003 in pancreatic cancer remain to be elucidated.Methods:Cell proliferation and apoptosis were detected using CCK-8,real-time cell analysis(RTCA),EdU,and flow cytometric assays.Cellular mobility and invasive capacity were detected using wound-healing,Transwell,and cell motility assays.Tumor growth and metastasis were determined using the mouse subcutaneous and pancreatic cancer orthotopic liver metastasis models.The antitumor effects of CLT-003 were evaluated using patient-derived organoid(PDO)and patient-derived xenograft(PDX)models.Results:CLT-003 significantly inhibited cellular proliferation,enhanced cellular apoptosis,and attenuated cellular invasion and migration of pancreatic cancer cells.Mechanistically,CLT-003 suppressed the translation of HIF-1a by inhibiting the PI3K/AKT/mTOR signaling pathway.In the mouse tumor models,CLT-003 significantly inhibited the growth and metastasis of pancreatic tumors.Moreover,the PDO and PDX models showed increased sensitivity to CLT-003 in pancreatic cancer with high HIF-1a expression compared to pancreatic cancer with low HIF-1a expression.Conclusions:This study delineated the role and molecular mechanism of CLT-003 action in impeding the progression of pancreatic cancer and indicated its robust potential for the treatment of pancreatic cancer.展开更多
基金supported by grants from the Seoul National University Bundang Hospital(SNUBH)Research Fund(Grant no.02-2020-0008)the Creative-Pioneering Researchers Program of Seoul National University(Grant no.860-20240109).
文摘Background:Oral cancer remains a significant global health challenge,as it has high morbidity and mortality rates.Current treatments show limited efficacy and have severe side effects,prompting searches for new therapeutic agents.SH003,a traditional herbal formulation comprising Astragalus membranaceus,Angelica gigas,and Trichosanthes kirilowii,has demonstrated potential anticancer properties in previous studies.However,its specific efficacy against oral cancer and the role of its key components,particularly Cucurbitacin D,remain underexplored.Methods:The cytotoxic effects of SH003 and its major components—i.e.,Cucurbitacin D,Decursin,Formononetin,and Nodakenin—were evaluated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide(MTT),Trypan Blue exclusion,and Lactate Dehydrogenase(LDH)release assays.Cell migration was analyzed via wound healing assays,and apoptosis induction was assessed using cell cycle analysis and caspase activation assays.Epithelial-tomesenchymal transition(EMT)marker expression(E-cadherin and N-cadherin)was measured using Western blotting and Quantitative reverse transcription PCR(qRT-PCR).Results:SH003 significantly reduced cell viability in a dosedependent manner,with YD-8 and YD-9 cells showing greater sensitivity than YD-38 cells.Of the individual compounds,Cucurbitacin D was identified as a key active agent,as it exhibited potent inhibition of cell migration and significant modulation of EMT markers,including the upregulation of E-cadherin and downregulation of N-cadherin.These effects were most pronounced in YD-9 cells.Conclusions:Taken together,these findings suggest that Cucurbitacin D plays a crucial role mediating the anticancer activity of SH003,particularly via the reversal of EMT and the reduction of migratory and invasive potential of oral cancer cells.This study provides valuable insight into the mechanistic basis of SH003,highlighting its potential as a therapeutic agent against oral cancer.Further research,including in vivo studies and clinical trials,is needed to elucidate its precise mechanisms and potential applications against other cancer types.
基金supported by the National Natural Science Foundation of China(Grant Nos.82472973,82030092,82273362,82272680,and 82103006)the National Key Research and Development Program of China(Grant No.2021YFA1201100)+2 种基金the Tianjin Natural Science Foundation(Grant Nos.19JCJQJC63100 and 22JCQNJC00100)the Science&Technology Development Fund of Tianjin Education Commission for Higher Education(Grant No.2022KJ221)the Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-009A).
文摘Objective:CLT-003 is a novel phenylphthalimide derivative encapsulated in poly(lactate-glycolic acid)copolymer nanoparticles using nanotechnology techniques.CLT-003 possesses anti-angiogenetic and antitumor activities.Nevertheless,the role and molecular mechanism underlying CLT-003 in pancreatic cancer remain to be elucidated.Methods:Cell proliferation and apoptosis were detected using CCK-8,real-time cell analysis(RTCA),EdU,and flow cytometric assays.Cellular mobility and invasive capacity were detected using wound-healing,Transwell,and cell motility assays.Tumor growth and metastasis were determined using the mouse subcutaneous and pancreatic cancer orthotopic liver metastasis models.The antitumor effects of CLT-003 were evaluated using patient-derived organoid(PDO)and patient-derived xenograft(PDX)models.Results:CLT-003 significantly inhibited cellular proliferation,enhanced cellular apoptosis,and attenuated cellular invasion and migration of pancreatic cancer cells.Mechanistically,CLT-003 suppressed the translation of HIF-1a by inhibiting the PI3K/AKT/mTOR signaling pathway.In the mouse tumor models,CLT-003 significantly inhibited the growth and metastasis of pancreatic tumors.Moreover,the PDO and PDX models showed increased sensitivity to CLT-003 in pancreatic cancer with high HIF-1a expression compared to pancreatic cancer with low HIF-1a expression.Conclusions:This study delineated the role and molecular mechanism of CLT-003 action in impeding the progression of pancreatic cancer and indicated its robust potential for the treatment of pancreatic cancer.
