OBJECTIVE: To test if myricanone (02H2405), a cyclic diarylheptanoid, has anticancer effects on two different cancer cell lines HeLa and PC3. The present study was conducted with a note on the drug-DNA interaction ...OBJECTIVE: To test if myricanone (02H2405), a cyclic diarylheptanoid, has anticancer effects on two different cancer cell lines HeLa and PC3. The present study was conducted with a note on the drug-DNA interaction and apoptotic signalling pathway. METHODS: Several studies like cytotoxicity, nuclear damage, annexin-V-fluorescein isothiocyanate (FITC)/propidium iodide (PI)-Iabelled apoptotic assay and cell cycle arrest, immunoblot and reverse transcriptase-polymerase chain reaction (RT-PCR) were used following standard protocols. Circular dichroism (CD) spectroscopy was also done to evaluate whether myricanone effectively interacted with DNA to bring about conformational changes that could strongly inhibit the cancer cell proliferation. RESULTS: Myricanone showed a greater cytotoxic effect on PC3 cells than on HeLa cells. Myricanone promoted G0/G arrest in HeLa cells and S phase arrest in PC3 cells. Nuclear condensation and annexin V-FITC/PI studies revealed that myricanone promoted apoptotic cell death. CD spectroscopic data indicated that myricanone had an interaction with calf thymus DNA that changed DNA structural conformation. RT-PCR and immunoblot studies revealed that myricanone activated the apoptotic signalling cascades through down-regulation of transcription factors like nuclear factor-KB (NF-KB) (p65), and signal transducers and activators of transcription 3 (STAT3); cell cycle regulators like cyclin D1, and survivin and other signal proteins like Bcl-2 and up-regulation of Bax, caspase-9 and caspase-3. CONCLUSION: Myricanone induced apoptosis in both types of cancer cells by triggering caspase activation, and suppression of cell proliferation by down-regulation of NF-KB and STAT3 signalling cascades, which makes it a suitable candidate for possible use in the formulation of therapeutic alent for combatin cancer.展开更多
OBJECTIVE: To provide in vitro evidence of Psorinum treatment against cancer cells in a controlled study. METHODS: Effects of homeopathic Psorinum 6× on cell viability were initially determined in several cance...OBJECTIVE: To provide in vitro evidence of Psorinum treatment against cancer cells in a controlled study. METHODS: Effects of homeopathic Psorinum 6× on cell viability were initially determined in several cancer cell lines, including A549, Hep G2 and MCF-7, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and an ethanol 6× control. The cell line that exhibited highest inhibition was selected and used in the following experiments. A range of Psorinum 6× doses was used to explore treatment effects on cell cycle arrest, cell death(apoptosis), generation of reactive oxygen species(ROS) and change in mitochondrial membrane potential(MMP) using fl ow cytometry and fl uorescence microscopy, respectively. Expression of several signal proteins related to apoptosis and cell survival were quantified with Western blotting and confocal microscopy. Further, circular dichroism(CD) spectroscopy was used to determine possible drug-DNA interactions, as well as the induction of conformational changes. RESULTS: Treatment of cancer cell lines with Psorinum showed greater anticancer effects in A549 cells than in others. In A549 cells Psorinum treatment inhibited cell proliferation at 24 h after treatment, and arrested cell cycle at sub-G1 stage. It also induced ROS generation, MMP depolarization, morphological changes and DNA damage, as well as externalization of phosphatidyl serine. Further, increases in p53 expression, Bax expression, cytochrome c release, along with reduction of Bcl-2 level and caspase-3 activation were observed after Psorinum 6× treatment, which eventually drove A549 cells towards the mitochondria-mediated caspase-3-dependent pathway. CD spectroscopy revealed direct interaction of Psorinum with DNA, using calf thymus-DNA as target.CONCLUSION: Psorinum 6× triggered apoptosis in A549 cells via both up- and down-regulations of relevant signal proteins, including p53, caspase-3, Bax and Bcl-2.展开更多
Diabetes is a chronic metabolic disorder that affects millions of people worldwide and takes a heavy toll on human life. Treatment of diabetics often poses a problem in selection of the proper drug, its dose and unwan...Diabetes is a chronic metabolic disorder that affects millions of people worldwide and takes a heavy toll on human life. Treatment of diabetics often poses a problem in selection of the proper drug, its dose and unwanted side effects. Therefore, newer drugs with the least side effects but with highest efficiency are being relentlessly searched for. In recent years, nanotechnology has given new hope for the formulation of various drugs against a myriad of diseases, including diabetes. This review tries to give an overview of the advantages of various new drugs being used, including a wide range of nanoformulations of orthodox as well complementary and alternative medicines. Several studies and research reports based on nanotechnological approaches in the formulation of anti-diabetic drugs have pointed out the fact that research in the formulation of nanodrugs improved strategies for combating diabetes based on the plausible molecular mechanism of action of the drugs. Furthermore, attempts have also been made to delineate the optimum drug concentration and time of exposure in order to recommend a scientifically validated drug dose response in developing different therapeutic strategies. Thus, to a considerable extent, recent studies have contributed towards improving thelife expectancy and quality of life of diabetics, through both targeted orthodox medicine and complementary medicine, particularly those obtained from natural resources.展开更多
Objectives:Pesticide toxicity has become one of the major environmental menaces affecting all types of life forms of the ecosystem.Pesticides get washed off from agricultural fields into nearby water bodies and enter ...Objectives:Pesticide toxicity has become one of the major environmental menaces affecting all types of life forms of the ecosystem.Pesticides get washed off from agricultural fields into nearby water bodies and enter the aquatic organisms.Their bio-accumulated form finally reaches the human race,through consumption of pesticide infested aquatic animals,causing several physiological dysfunctions.Hence it becomes necessary to find a therapeutic cure/a preventive measure to stop the health hazard issues of pesticide.With this projection a search for a phyto-based-product was made whose primary objective would be to lower the pesticidal toxicity in fish and simultaneously in the human race.Methods:In this study we tried to check whether the phyto-chemical,Chlorophyllin(CHL),known for its anti-genotoxic,anti-oxidant activities,could render any kind of protection against Cypermethrin(CM)induced-toxicity in fish model and mammalian cell line L6.Both the model L6 and fish were pre-treated with CHL prior to exposure of CM.Different scientific parameters like%cellular cytotoxicity,reactive oxygen species(ROS)generation,nuclear condensation,etc were checked to validate the possibility of CHL in protecting CM-induced toxicity.Results:The overall results revealed that pre-treatment with CHL could restrict the ROS generation leading to modulation in associated cytokine proteins expression NFkβand IFNγ.Further,CHL lowered nuclear condensation and elevated expression of DNA repair proteins p53 and PARP,showing a kind of pre-activation of signalling cascades for overall protection against the severity of pesticidal toxicity.Conclusion:Thus,this phyto-based preventive approach would possibly solve many areas of human health issues related to pesticide toxicity in future.展开更多
基金partially supported by a grant sanctioned to Prof.A.R.Khuda-Bukhsh,Department of Zoology, University of Kalyani,India,by Boiron Laboratories, Lyon,France
文摘OBJECTIVE: To test if myricanone (02H2405), a cyclic diarylheptanoid, has anticancer effects on two different cancer cell lines HeLa and PC3. The present study was conducted with a note on the drug-DNA interaction and apoptotic signalling pathway. METHODS: Several studies like cytotoxicity, nuclear damage, annexin-V-fluorescein isothiocyanate (FITC)/propidium iodide (PI)-Iabelled apoptotic assay and cell cycle arrest, immunoblot and reverse transcriptase-polymerase chain reaction (RT-PCR) were used following standard protocols. Circular dichroism (CD) spectroscopy was also done to evaluate whether myricanone effectively interacted with DNA to bring about conformational changes that could strongly inhibit the cancer cell proliferation. RESULTS: Myricanone showed a greater cytotoxic effect on PC3 cells than on HeLa cells. Myricanone promoted G0/G arrest in HeLa cells and S phase arrest in PC3 cells. Nuclear condensation and annexin V-FITC/PI studies revealed that myricanone promoted apoptotic cell death. CD spectroscopic data indicated that myricanone had an interaction with calf thymus DNA that changed DNA structural conformation. RT-PCR and immunoblot studies revealed that myricanone activated the apoptotic signalling cascades through down-regulation of transcription factors like nuclear factor-KB (NF-KB) (p65), and signal transducers and activators of transcription 3 (STAT3); cell cycle regulators like cyclin D1, and survivin and other signal proteins like Bcl-2 and up-regulation of Bax, caspase-9 and caspase-3. CONCLUSION: Myricanone induced apoptosis in both types of cancer cells by triggering caspase activation, and suppression of cell proliferation by down-regulation of NF-KB and STAT3 signalling cascades, which makes it a suitable candidate for possible use in the formulation of therapeutic alent for combatin cancer.
文摘OBJECTIVE: To provide in vitro evidence of Psorinum treatment against cancer cells in a controlled study. METHODS: Effects of homeopathic Psorinum 6× on cell viability were initially determined in several cancer cell lines, including A549, Hep G2 and MCF-7, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and an ethanol 6× control. The cell line that exhibited highest inhibition was selected and used in the following experiments. A range of Psorinum 6× doses was used to explore treatment effects on cell cycle arrest, cell death(apoptosis), generation of reactive oxygen species(ROS) and change in mitochondrial membrane potential(MMP) using fl ow cytometry and fl uorescence microscopy, respectively. Expression of several signal proteins related to apoptosis and cell survival were quantified with Western blotting and confocal microscopy. Further, circular dichroism(CD) spectroscopy was used to determine possible drug-DNA interactions, as well as the induction of conformational changes. RESULTS: Treatment of cancer cell lines with Psorinum showed greater anticancer effects in A549 cells than in others. In A549 cells Psorinum treatment inhibited cell proliferation at 24 h after treatment, and arrested cell cycle at sub-G1 stage. It also induced ROS generation, MMP depolarization, morphological changes and DNA damage, as well as externalization of phosphatidyl serine. Further, increases in p53 expression, Bax expression, cytochrome c release, along with reduction of Bcl-2 level and caspase-3 activation were observed after Psorinum 6× treatment, which eventually drove A549 cells towards the mitochondria-mediated caspase-3-dependent pathway. CD spectroscopy revealed direct interaction of Psorinum with DNA, using calf thymus-DNA as target.CONCLUSION: Psorinum 6× triggered apoptosis in A549 cells via both up- and down-regulations of relevant signal proteins, including p53, caspase-3, Bax and Bcl-2.
文摘Diabetes is a chronic metabolic disorder that affects millions of people worldwide and takes a heavy toll on human life. Treatment of diabetics often poses a problem in selection of the proper drug, its dose and unwanted side effects. Therefore, newer drugs with the least side effects but with highest efficiency are being relentlessly searched for. In recent years, nanotechnology has given new hope for the formulation of various drugs against a myriad of diseases, including diabetes. This review tries to give an overview of the advantages of various new drugs being used, including a wide range of nanoformulations of orthodox as well complementary and alternative medicines. Several studies and research reports based on nanotechnological approaches in the formulation of anti-diabetic drugs have pointed out the fact that research in the formulation of nanodrugs improved strategies for combating diabetes based on the plausible molecular mechanism of action of the drugs. Furthermore, attempts have also been made to delineate the optimum drug concentration and time of exposure in order to recommend a scientifically validated drug dose response in developing different therapeutic strategies. Thus, to a considerable extent, recent studies have contributed towards improving thelife expectancy and quality of life of diabetics, through both targeted orthodox medicine and complementary medicine, particularly those obtained from natural resources.
基金Grateful acknowledgements are extended to SERB(DST)(ECR/2017/000355),UGC-BSR Start-up grant for providing nesearch funds which was used partly to accomplish this piece of workAuthors thank University of Kalyani(PRG and DST-PURSE)for their minor research funding which was used for the pupose of this work.
文摘Objectives:Pesticide toxicity has become one of the major environmental menaces affecting all types of life forms of the ecosystem.Pesticides get washed off from agricultural fields into nearby water bodies and enter the aquatic organisms.Their bio-accumulated form finally reaches the human race,through consumption of pesticide infested aquatic animals,causing several physiological dysfunctions.Hence it becomes necessary to find a therapeutic cure/a preventive measure to stop the health hazard issues of pesticide.With this projection a search for a phyto-based-product was made whose primary objective would be to lower the pesticidal toxicity in fish and simultaneously in the human race.Methods:In this study we tried to check whether the phyto-chemical,Chlorophyllin(CHL),known for its anti-genotoxic,anti-oxidant activities,could render any kind of protection against Cypermethrin(CM)induced-toxicity in fish model and mammalian cell line L6.Both the model L6 and fish were pre-treated with CHL prior to exposure of CM.Different scientific parameters like%cellular cytotoxicity,reactive oxygen species(ROS)generation,nuclear condensation,etc were checked to validate the possibility of CHL in protecting CM-induced toxicity.Results:The overall results revealed that pre-treatment with CHL could restrict the ROS generation leading to modulation in associated cytokine proteins expression NFkβand IFNγ.Further,CHL lowered nuclear condensation and elevated expression of DNA repair proteins p53 and PARP,showing a kind of pre-activation of signalling cascades for overall protection against the severity of pesticidal toxicity.Conclusion:Thus,this phyto-based preventive approach would possibly solve many areas of human health issues related to pesticide toxicity in future.