论文部分内容阅读
Human cancer is a severe malignancy and global health problem.Chemotherapy has beenconsidered promising therapy for the treatment of human cancers.However, prolong treatment ofchemotherapy leads to clonal evolution owing to novel mutations and results in resistance in responseto novel anti-cancer drugs.Medermycin, as a prominent member of benzoisochromanequinones,possesses strong antitumor activity and is biosynthesized under the control of a 29-ORFcontainingbiosynthetic gene cluster.Most of ORFs in this gene cluster have not been characterized, including asmall protein encoding gene med-ORF10, proposed to play a regulatory role in biosynthesis ofmedermycin in an unknown mode.In our first experiment, we reported the expression, proteinpreparation, crystallization and preliminary X-ray diffraction analyses of Med-ORF10 of the wild typeStreptomyees strain.These studies provide evidences for the functional Med-ORF10 protein inStreptomyees strains and facilitate our further investigation.
Mitoehondria dynamic is also strongly associated with cancer progression and suppression throughfission and fusion.Mitoehondrial fission causes cancer progression whereas mitochondrial fusionsuppresses cancer.Mitoehondrial fission and fusion are mediated by various GTPases in outermitoehondrial membrane, particularly mitofusin-1 (Mfn-1) and mitofusin-2 (Mfn-2), which inducesfusion, and dynamin-related protein (Drp-1), which induces fission.In our second experiment, weexplored the potential role of SPRYD4 gene in cancer suppression through modulating mitochondrialdynamics.We found that overexpression of SPRYD4 causes decreased fission and increased fusion incancer cells via unbalancing expression of fission and fusion regulators.Overexpressed SPRYD4HeLa cells demonstrated a decrease in Drp-1 and an increase in Mfn-1 and Mfn-2 as compared to WTHeLa cells.Furthermore, overexpression of SPRYD4 suppresses cancer cell proliferation and energyproduction.Loss of SPRYD4 compromises mitoehondrial fragmentation in cancer cells.Takentogether, these findings suggested that SPRYD4 plays an important role in the suppression of cancerprogression through modulating mitochondrial dynamics.
Currently, impairing energy metabolism has been viewed as an effective and promising antieancerstrategy.Flavaglines are potent anticancer natural products that inhibit cancer cells proliferation andviability at a nanomolar concentration without being toxic to non-cancer tissues.In our thirdexperiment, we explored the effects of FL3, a synthetic flabagline, on cancer energy metabolism.
Results show that FL3 inhibited cancer cell proliferation by inhibiting energy production and inducingcell cycle arrest.
In conclusion, this study has explored molecular meehasnisms of cancer progression drug resistanceand novel approaches for overcoming drug resistance to novel anti-cancer drugs.This study will opena new window in improving currently used therapeutic tools and developing new strategies fortreating human cancers.
Mitoehondria dynamic is also strongly associated with cancer progression and suppression throughfission and fusion.Mitoehondrial fission causes cancer progression whereas mitochondrial fusionsuppresses cancer.Mitoehondrial fission and fusion are mediated by various GTPases in outermitoehondrial membrane, particularly mitofusin-1 (Mfn-1) and mitofusin-2 (Mfn-2), which inducesfusion, and dynamin-related protein (Drp-1), which induces fission.In our second experiment, weexplored the potential role of SPRYD4 gene in cancer suppression through modulating mitochondrialdynamics.We found that overexpression of SPRYD4 causes decreased fission and increased fusion incancer cells via unbalancing expression of fission and fusion regulators.Overexpressed SPRYD4HeLa cells demonstrated a decrease in Drp-1 and an increase in Mfn-1 and Mfn-2 as compared to WTHeLa cells.Furthermore, overexpression of SPRYD4 suppresses cancer cell proliferation and energyproduction.Loss of SPRYD4 compromises mitoehondrial fragmentation in cancer cells.Takentogether, these findings suggested that SPRYD4 plays an important role in the suppression of cancerprogression through modulating mitochondrial dynamics.
Currently, impairing energy metabolism has been viewed as an effective and promising antieancerstrategy.Flavaglines are potent anticancer natural products that inhibit cancer cells proliferation andviability at a nanomolar concentration without being toxic to non-cancer tissues.In our thirdexperiment, we explored the effects of FL3, a synthetic flabagline, on cancer energy metabolism.
Results show that FL3 inhibited cancer cell proliferation by inhibiting energy production and inducingcell cycle arrest.
In conclusion, this study has explored molecular meehasnisms of cancer progression drug resistanceand novel approaches for overcoming drug resistance to novel anti-cancer drugs.This study will opena new window in improving currently used therapeutic tools and developing new strategies fortreating human cancers.