Over recent decades, many studies have reported that hypocrellin A(HA) can eliminate cancer cells with proper irradiation in several cancer cell lines. However, the precise molecular mechanism underlying its anticance...Over recent decades, many studies have reported that hypocrellin A(HA) can eliminate cancer cells with proper irradiation in several cancer cell lines. However, the precise molecular mechanism underlying its anticancer effect has not been fully defined. HA-mediated cytotoxicity and apoptosis in human lung adenocarcinoma A549 cells were evaluated after photodynamic therapy(PDT). A temporal quantitative proteomics approach by isobaric tag for relative and absolute quantitation(iTRAQ) 2 D liquid chromatography with tandem mass spectrometric(LC–MS/MS) was introduced to help clarify molecular cytotoxic mechanisms and identify candidate targets of HA-induced apoptotic cell death. Specific caspaseinhibitors were used to further elucidate the molecular pathway underlying apoptosis in PDT-treated A549 cells. Finally, down-stream apoptosis-related protein was evaluated. Apoptosis induced by HA was associated with cell shrinkage, externalization of cell membrane phosphatidylserine, DNA fragmentation,and mitochondrial disruption, which were preceded by increased intracellular reactive oxygen species(ROS) generations. Further studies showed that PDT treatment with 0.08 mmol/L HA resulted in mitochondrial disruption, pronounced release of cytochrome c, and activation of caspase-3,-9, and-7.Together, HA may be a possible therapeutic agent directed toward mitochondria and a promising photodynamic anticancer candidate for further evaluation.展开更多
Hypocrellin A（ HA）, a photosensitive perylenequinone compound of Hypocrella bambusae, inhibited the proliferation of several tumor cell lines. Human cervical cancer cells, HeLa ceils, were used as a model to elucida...Hypocrellin A（ HA）, a photosensitive perylenequinone compound of Hypocrella bambusae, inhibited the proliferation of several tumor cell lines. Human cervical cancer cells, HeLa ceils, were used as a model to elucidate the molecular mechanisms of HA-induced tumor cell death. The results show that HA can induce the oligonucleosomal fragmentation of DNA in HeLa cells and also can increase the expression of apoptosis inducer Bax mRNA and that it decreases the expression of apoptosis suppressor, Bcl-2 mRNA, in mitochondria. It can be concluded from the data that HA-induced apoptosis is related to the balance between Bcl-2 and Bax gene expressions.展开更多
Laser Raman spectroscopy provided the direct evidence for microcosmic photodamage in space structure of DNA molecule. When photosensitive damage was made to space structure of calf thymus DNA by hypocrellins A and B, ...Laser Raman spectroscopy provided the direct evidence for microcosmic photodamage in space structure of DNA molecule. When photosensitive damage was made to space structure of calf thymus DNA by hypocrellins A and B, the Raman characteristic frequencies and the intensities of the bands assigned to various groups of the components of DNA (phosphate backbone deoxyribose and four bases) changed at various degrees. There were not only the strand breakage, but also the breakage of some H bonds and disruption of vertical base base stacking interactions. The photosensitive damage of hypocrellin B on DNA was stronger than that of hypocrellin A on DNA.展开更多
基金supported by the National Natural Science Foundation of China(Project No.81673214)The National Key Technology Research and National Key Technology Research and Development Program of the Ministry of Science and Technology of the People's Republic of China(Project No.2012BAD36B0502)the Priority Academic Program Development of Jiangsu Higher Educational Institutions(China)
文摘Over recent decades, many studies have reported that hypocrellin A(HA) can eliminate cancer cells with proper irradiation in several cancer cell lines. However, the precise molecular mechanism underlying its anticancer effect has not been fully defined. HA-mediated cytotoxicity and apoptosis in human lung adenocarcinoma A549 cells were evaluated after photodynamic therapy(PDT). A temporal quantitative proteomics approach by isobaric tag for relative and absolute quantitation(iTRAQ) 2 D liquid chromatography with tandem mass spectrometric(LC–MS/MS) was introduced to help clarify molecular cytotoxic mechanisms and identify candidate targets of HA-induced apoptotic cell death. Specific caspaseinhibitors were used to further elucidate the molecular pathway underlying apoptosis in PDT-treated A549 cells. Finally, down-stream apoptosis-related protein was evaluated. Apoptosis induced by HA was associated with cell shrinkage, externalization of cell membrane phosphatidylserine, DNA fragmentation,and mitochondrial disruption, which were preceded by increased intracellular reactive oxygen species(ROS) generations. Further studies showed that PDT treatment with 0.08 mmol/L HA resulted in mitochondrial disruption, pronounced release of cytochrome c, and activation of caspase-3,-9, and-7.Together, HA may be a possible therapeutic agent directed toward mitochondria and a promising photodynamic anticancer candidate for further evaluation.
基金Supported by the Department of Science and Technology of Jilin Province(No.20020502).
文摘Hypocrellin A（ HA）, a photosensitive perylenequinone compound of Hypocrella bambusae, inhibited the proliferation of several tumor cell lines. Human cervical cancer cells, HeLa ceils, were used as a model to elucidate the molecular mechanisms of HA-induced tumor cell death. The results show that HA can induce the oligonucleosomal fragmentation of DNA in HeLa cells and also can increase the expression of apoptosis inducer Bax mRNA and that it decreases the expression of apoptosis suppressor, Bcl-2 mRNA, in mitochondria. It can be concluded from the data that HA-induced apoptosis is related to the balance between Bcl-2 and Bax gene expressions.
文摘Laser Raman spectroscopy provided the direct evidence for microcosmic photodamage in space structure of DNA molecule. When photosensitive damage was made to space structure of calf thymus DNA by hypocrellins A and B, the Raman characteristic frequencies and the intensities of the bands assigned to various groups of the components of DNA (phosphate backbone deoxyribose and four bases) changed at various degrees. There were not only the strand breakage, but also the breakage of some H bonds and disruption of vertical base base stacking interactions. The photosensitive damage of hypocrellin B on DNA was stronger than that of hypocrellin A on DNA.
