OBJECTIVE:To investigate the antitumor effects of bornyl acetate(BA)isolated from Sharen(Fructus Amomi)in colorectal cancer(CRC)and the underlying mechanisms.METHODS:SW480 and HT29 cells were treated with increasing d...OBJECTIVE:To investigate the antitumor effects of bornyl acetate(BA)isolated from Sharen(Fructus Amomi)in colorectal cancer(CRC)and the underlying mechanisms.METHODS:SW480 and HT29 cells were treated with increasing doses of BA in order to determine its antitumor effects in vitro.Cell viability,colony formation,cell cycle,and apoptosis as well as migration and invasion were assessed using various assays.In addition,the in vivo antitumor effects of BA were assessed using a xenograft mouse model.We then assessed the mechanism of action of BA by conducting pathway activator-mediated rescue experiments and assessed the protein levels by Western blot analysis.RESULTS:BA showed anti-CRC tumor activities in vitro by suppressing cell proliferation and colony formation,inducing apoptosis,blocking cell cycle,and inhibiting migration and invasion.These effects were mediated via suppression of the phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)pathway.In the tumor xenograft experiment,BA was found to repress tumor growth in vivo with low toxicity.CONCLUSIONS:The results demonstrated that BA exerts antitumor effects by suppressing the PI3K/AKT pathway,with low toxicity.Thus,BA might be a potential novel therapeutic agent for CRC.展开更多
Gastrointestinal tract toxicity represents a serious adverse effect of chemotherapy,leading to reduced quality of life and survival.For instance,irinotecan(CPT-11)usually causes severe gastrointestinal toxicity,with a...Gastrointestinal tract toxicity represents a serious adverse effect of chemotherapy,leading to reduced quality of life and survival.For instance,irinotecan(CPT-11)usually causes severe gastrointestinal toxicity,with a lack of effective therapeutic interventions,making treatment often unsustainable.Therefore,development of an effective and safe therapy is crucial for improving chemotherapy efficacy and the patients’quality of life.In this work,we developed a novel approach involving the helical-shaped cyanobacterium microalgae,Spirulina platensis(SP),to carry the bornyl acetate(BA)-loaded chitosan nanoparticles to enhance drug retention in the small intestine.We demonstrated the protection effect of BA against chemotherapy-induced intestinal injury using an epithelial cell model.In a mouse model,orally administered BA-ChNPs@SP accumulated in the small intestine and attenuated inflammation by reducing dsDNA release and oxidative stress.This was concomitant with the restoration of the intestinal barrier and modulation of the immune microenvironment.This work suggests the promise of the microalgae-carrying nanomedicine strategy for treatment of intestinal diseases,emphasizing its potential in addressing chemotherapy-induced gastrointestinal complications.展开更多
基金National Key R&D Program of China:Underground Ecological Planting Technology and Base Establishment of Sharen (Fructus Amomi) in the forest (2017YFC1701102)West Yunnan University of Applied Sciences University-level Engineering Research Center projects:Characteristic Dai-Medicine Resource ERC of West Yunnan University of Apllied Science (2022KYPT0004)+3 种基金National Natural Science Foundation of China:Study on the symbiotic system of Sharen (Fructus Amomi)weevil pollination and its "push-pull" pollination mechanism (82260736)Yunnan key labotatory of southern medicine utilization:Major Science and Technology Special Plan of Yunnan Province (202102AA100020)Scientific and Technological Talents and Platform Plan of Yunnan Province (202105AG070011)
文摘OBJECTIVE:To investigate the antitumor effects of bornyl acetate(BA)isolated from Sharen(Fructus Amomi)in colorectal cancer(CRC)and the underlying mechanisms.METHODS:SW480 and HT29 cells were treated with increasing doses of BA in order to determine its antitumor effects in vitro.Cell viability,colony formation,cell cycle,and apoptosis as well as migration and invasion were assessed using various assays.In addition,the in vivo antitumor effects of BA were assessed using a xenograft mouse model.We then assessed the mechanism of action of BA by conducting pathway activator-mediated rescue experiments and assessed the protein levels by Western blot analysis.RESULTS:BA showed anti-CRC tumor activities in vitro by suppressing cell proliferation and colony formation,inducing apoptosis,blocking cell cycle,and inhibiting migration and invasion.These effects were mediated via suppression of the phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)pathway.In the tumor xenograft experiment,BA was found to repress tumor growth in vivo with low toxicity.CONCLUSIONS:The results demonstrated that BA exerts antitumor effects by suppressing the PI3K/AKT pathway,with low toxicity.Thus,BA might be a potential novel therapeutic agent for CRC.
基金the National Key Research and Development Program of China(2022YFE0203600,China)NFSC(81925035,82341232)+2 种基金Program of Shanghai Committee of Science and Technology(21ZR1475200,China)Department of Science and Technology of Guangdong Province(High-Level R&D and Innovative Research Institute 2021B0909050003)SciTech Projects of Zhongshan(CXTD2022011,LJ2021001).
文摘Gastrointestinal tract toxicity represents a serious adverse effect of chemotherapy,leading to reduced quality of life and survival.For instance,irinotecan(CPT-11)usually causes severe gastrointestinal toxicity,with a lack of effective therapeutic interventions,making treatment often unsustainable.Therefore,development of an effective and safe therapy is crucial for improving chemotherapy efficacy and the patients’quality of life.In this work,we developed a novel approach involving the helical-shaped cyanobacterium microalgae,Spirulina platensis(SP),to carry the bornyl acetate(BA)-loaded chitosan nanoparticles to enhance drug retention in the small intestine.We demonstrated the protection effect of BA against chemotherapy-induced intestinal injury using an epithelial cell model.In a mouse model,orally administered BA-ChNPs@SP accumulated in the small intestine and attenuated inflammation by reducing dsDNA release and oxidative stress.This was concomitant with the restoration of the intestinal barrier and modulation of the immune microenvironment.This work suggests the promise of the microalgae-carrying nanomedicine strategy for treatment of intestinal diseases,emphasizing its potential in addressing chemotherapy-induced gastrointestinal complications.
