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) 2D 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 caspase inhibitors 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 µmol/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.

在最近的几十年中，许多研究报告说，hypercrellin A（HA）可以通过适当照射在几种癌细胞系中消除癌细胞。但是，其抗癌作用的确切分子机制尚未完全确定。光动力学治疗（PDT）后评估HA介导的人肺腺癌A549细胞的细胞毒性和凋亡。通过等压标记的时间定量蛋白质组学方法，采用串联质谱（LC-MS / MS）进行了相对和绝对定量（iTRAQ）二维液相色谱（LC-MS / MS），以帮助阐明分子细胞毒性机制并确定HA诱导的凋亡细胞死亡的候选靶标。使用特定的半胱天冬酶抑制剂进一步阐明了PDT处理的A549细胞凋亡的分子途径。最后，评估下游凋亡相关蛋白。HA诱导的细胞凋亡与细胞萎缩，细胞膜磷脂酰丝氨酸的外在化，DNA片段化和线粒体破坏有关，随后细胞内活性氧（ROS）生成增加。进一步的研究表明，用0.08 µmol / L HA进行PDT处理会导致线粒体破坏，显着释放细胞色素c以及caspase-3，-9和-7的激活。总之，HA可能是针对线粒体的可能治疗剂，并且是有前途的光动力抗癌候选药物，可以进一步评估。