Withaferin A (WA) is a bioactive compound derived from a medicinal plant Withania somnifera and has potential therapeutic effects against various types of cancers. The purpose of this study is to investigate an apopto...Withaferin A (WA) is a bioactive compound derived from a medicinal plant Withania somnifera and has potential therapeutic effects against various types of cancers. The purpose of this study is to investigate an apoptotic effect of WA and identify its molecular target in HSC-3 and HSC-4 human oral cancer cell lines using Trypan blue exclusion assay, DAPI staining and western blotting. WA inhibited cell viability and induced apoptosis in a concentration- or time-dependent manner, as evidenced by induction of nuclear condensation and fragmentation, activation of caspase 3 and poly (ADP-ribose) polymerase (PARP) cleavage. WA-induced apoptosis was partly diminished by Z-VAD, a pancaspase inhibitor. WA also increased Bim and Bax protein in HSC-3 and HSC-4 cells, respectively. These results suggest that WA may be a potential chemotherapeutic drug candidate against human oral cancer.展开更多
Aim:As our understanding of cancer stem cell(CSC)biology improves,search for inhibitory agents of CSCs and metastatic CSCs(mCSCs)positive for CXCR4 is warranted.Withaferin A(WA),a withanolide extracted from the medici...Aim:As our understanding of cancer stem cell(CSC)biology improves,search for inhibitory agents of CSCs and metastatic CSCs(mCSCs)positive for CXCR4 is warranted.Withaferin A(WA),a withanolide extracted from the medicinal plant Withania somnifera,has been shown to exhibit anti-cancer effects through multiple mechanisms.Whether WA could selectively target CSCs,mCSCs,or non CSCs of a gastrointestinal(GI)carcinoma tumor remains unclear.Methods:Side-population(SP)analysis,flow cytometric phenotyping and sorting,non-invasive imaging in conjunction with xenotransplantation,and immunohistology were used in this investigation.Results:Using the lymph node metastatic GI cancer cell line UP-LN1,consisting of CD44^(high)/CD24^(low)floating(F)and CD44^(low)/CD24^(high)adherent(A)cell subsets,this study demonstrated that as compared with parental UP-LN1 cells or A cells,WA preferentially reduced F-cell proliferation,tumor sphere formation,and SP cells in vitro in greater effi ciencies by apoptosis.This action was mechanistically mediated via the down-regulation of CXCR4/CXCL12 and STAT3/interleukin-6 axes,both of which are instrumental in the acquisition of metastatic ability.Attenuation of interferon-γ-induced CXCR4 expression in F cells by knockdown with siRNA or blocking with an anti-CXCR4 antibody,followed by Western blot analysis,showed signifi cantly reduced metastatic potential in vitro.The extent of in vitro anti-invasive effect of WA on the IFN-γ-treated F cells was signifi cantly greater than on the F cells without WA treatment,or F cells treated with control siRNA or with control IgG antibody.The observed in vitro effects of WA on the CSC and mCSC targeting were validated by data obtained with non-invasive imaging in NOD/SCID mouse xenotransplantation.Conclusion:WA could effi ciently block the formation of both CSCs and mCSCs in the UP-LN1 cell line,suggesting that WA may be considered an effective therapeutic agent for this type of GI malignancies.展开更多
A combination therapy is discussed for the treatment of cancer, which has recently been applied successfully in a case study. The general approach is based on a combination of immune boosters, digestive enzymes and na...A combination therapy is discussed for the treatment of cancer, which has recently been applied successfully in a case study. The general approach is based on a combination of immune boosters, digestive enzymes and natural interferones. The idea is to stage a three-prong “pincer attack” on the tumor: while the immune boosters stimulate the immune system to attack cancer cells, the cytostatic properties of the interferones inhibit cancer growth, and the digestive enzymes accelerate the transport mechanism to remove the killed cancer cells from the body. The rationale of the therapy is explained, results of the case study are presented, and possible generalizations are mentioned.展开更多
Phytochemicals derived from dietary sources and natural products have gained significant attention in the scientific community due to their ability to modulate various pharmacological and biological activities.Underst...Phytochemicals derived from dietary sources and natural products have gained significant attention in the scientific community due to their ability to modulate various pharmacological and biological activities.Understanding the molecular mechanisms by which natural products protect against various diseases including cancer will provide the basis for both clinical use and further chemical modification to develop targeted therapy.Autophagy,an evolutionarily conserved self-digestion process that employs lysosomal-mediated enzymatic degradation has a functional role in a wide range of pathological disorders,and has attracted oncology scientists over the past two decades.Studies employing natural products have shown that induction of autophagy may be either cytoprotective or cytotoxic governed by different molecular pathways.In this review,we summarize four major phytochemicals namely phenethyl isothiocyanate,capsaicin,withaferin A,genistein and their association with autophagy in cancer chemoprevention.We also discuss ideas for further investigation essential to understanding their mechanisms,which will guide their clinical applications for cancer prevention and treatment.展开更多
文摘Withaferin A (WA) is a bioactive compound derived from a medicinal plant Withania somnifera and has potential therapeutic effects against various types of cancers. The purpose of this study is to investigate an apoptotic effect of WA and identify its molecular target in HSC-3 and HSC-4 human oral cancer cell lines using Trypan blue exclusion assay, DAPI staining and western blotting. WA inhibited cell viability and induced apoptosis in a concentration- or time-dependent manner, as evidenced by induction of nuclear condensation and fragmentation, activation of caspase 3 and poly (ADP-ribose) polymerase (PARP) cleavage. WA-induced apoptosis was partly diminished by Z-VAD, a pancaspase inhibitor. WA also increased Bim and Bax protein in HSC-3 and HSC-4 cells, respectively. These results suggest that WA may be a potential chemotherapeutic drug candidate against human oral cancer.
基金supported by grants from the National Science Council of Taiwan(NSC99-2314-B-038-032,NSC100-2314-B-038-016 to SK Liao)Chang Gung Medical Research Fund(CMRPD170043,CMRPG3A0811 to ST Pang and SK Liao).
文摘Aim:As our understanding of cancer stem cell(CSC)biology improves,search for inhibitory agents of CSCs and metastatic CSCs(mCSCs)positive for CXCR4 is warranted.Withaferin A(WA),a withanolide extracted from the medicinal plant Withania somnifera,has been shown to exhibit anti-cancer effects through multiple mechanisms.Whether WA could selectively target CSCs,mCSCs,or non CSCs of a gastrointestinal(GI)carcinoma tumor remains unclear.Methods:Side-population(SP)analysis,flow cytometric phenotyping and sorting,non-invasive imaging in conjunction with xenotransplantation,and immunohistology were used in this investigation.Results:Using the lymph node metastatic GI cancer cell line UP-LN1,consisting of CD44^(high)/CD24^(low)floating(F)and CD44^(low)/CD24^(high)adherent(A)cell subsets,this study demonstrated that as compared with parental UP-LN1 cells or A cells,WA preferentially reduced F-cell proliferation,tumor sphere formation,and SP cells in vitro in greater effi ciencies by apoptosis.This action was mechanistically mediated via the down-regulation of CXCR4/CXCL12 and STAT3/interleukin-6 axes,both of which are instrumental in the acquisition of metastatic ability.Attenuation of interferon-γ-induced CXCR4 expression in F cells by knockdown with siRNA or blocking with an anti-CXCR4 antibody,followed by Western blot analysis,showed signifi cantly reduced metastatic potential in vitro.The extent of in vitro anti-invasive effect of WA on the IFN-γ-treated F cells was signifi cantly greater than on the F cells without WA treatment,or F cells treated with control siRNA or with control IgG antibody.The observed in vitro effects of WA on the CSC and mCSC targeting were validated by data obtained with non-invasive imaging in NOD/SCID mouse xenotransplantation.Conclusion:WA could effi ciently block the formation of both CSCs and mCSCs in the UP-LN1 cell line,suggesting that WA may be considered an effective therapeutic agent for this type of GI malignancies.
文摘A combination therapy is discussed for the treatment of cancer, which has recently been applied successfully in a case study. The general approach is based on a combination of immune boosters, digestive enzymes and natural interferones. The idea is to stage a three-prong “pincer attack” on the tumor: while the immune boosters stimulate the immune system to attack cancer cells, the cytostatic properties of the interferones inhibit cancer growth, and the digestive enzymes accelerate the transport mechanism to remove the killed cancer cells from the body. The rationale of the therapy is explained, results of the case study are presented, and possible generalizations are mentioned.
文摘Phytochemicals derived from dietary sources and natural products have gained significant attention in the scientific community due to their ability to modulate various pharmacological and biological activities.Understanding the molecular mechanisms by which natural products protect against various diseases including cancer will provide the basis for both clinical use and further chemical modification to develop targeted therapy.Autophagy,an evolutionarily conserved self-digestion process that employs lysosomal-mediated enzymatic degradation has a functional role in a wide range of pathological disorders,and has attracted oncology scientists over the past two decades.Studies employing natural products have shown that induction of autophagy may be either cytoprotective or cytotoxic governed by different molecular pathways.In this review,we summarize four major phytochemicals namely phenethyl isothiocyanate,capsaicin,withaferin A,genistein and their association with autophagy in cancer chemoprevention.We also discuss ideas for further investigation essential to understanding their mechanisms,which will guide their clinical applications for cancer prevention and treatment.
