Taken together, this present study suggests that GRP78 plays an important role in protecting glial cells against H2O2 toxicity by regulating GSH and NQO1 expression. However, there are several pathways and factors related to GRP78 expression in cells and further studies are required to understand the mechanisms involved and the direct relationship between GRP78, GSH and NQO1 in order for molecular/pharmacological treatments of neurotrauma or neurodegenerative diseases to be developed. Head and neck cancer is one of the most common cancers in the world and one of causes of cancer-related death due to frequent recurrence after chemotherapy resistance. Despite improvements in the diagnosis and management of HNC, longterm survival rates have improved only marginally over the past decade. New drugs or Cryptochlorogenic-acid strategies are urgently needed to improve the chemosensitization to conventional chemotherapeutic drugs and clinical responses of HNC patients. Photodynamic therapy involves two individually nontoxic components, light and photosensitizer. PDT is a new treatment and holds considerable promise for many solid tumors. Studies have demonstrated that topical 5-aminolevulinic acid-mediated PDT is being used in the treatment of Senegenin various human premalignant and malignant lesions with some encouraging clinical outcomes. PDT might have the potential of inhibiting the metastasis of incompletely treated HNC. In a mice Lewis lung carcinoma model, ALAPDT decreased the metastasis of cancer cells in vivo. In addition, ALA-PDT increases apoptotic ability of oral cancer cells through NF-kB/JNK signaling. ALA-PDT also abrogated migration capacity of oral cancer cells by down-regulation of FAK and ERK. CSCs are considered to be responsible for the initiation, propagation and metastasis of tumors. Importantly, the existence of CSCs might explain cancer recurrences, even after clinical treatment with either radiotherapy or chemotherapy on cancer patients. Therefore, searching the novel treatment strategy targeting CSCs hopefully provide us with new therapeutic approaches. In the present report, we firstly showed ALA-PDT provided a therapeutic effect in HNC-CSCs by inhibiting the CSCs-like properties of head and neck cancer, such as the stemness signature, migration ability, and chemoresistance. To the best of our knowledge, this is the first study to demonstrate the critical role of an ALA-PDT-based therapy in targeting HNCderived CSC-like cells and in blocking HNC-CSCs-mediated tumor initiating activity. Epithelial-mesenchymal transition is a process critical for appropriate embryonic development, and it is also re-engaged in adults during tumorigenesis. EMT is widely accepted as one of the CSCs properties, and Oct4/Nanog signaling has been demonstrated to be involved in the regulation of EMT and metastasis. Oral cancer epithelial cells can acquire mesenchymal traits which facilitate migration and invasion through EMT process. It is known that EMT can give rise to cells 
with stem cell, and cancer initiating stem cells properties that have undergone EMT are therefore more motile and metastasized.. Since we have found that the effect of ALA-PDT on invasion ability in HNC-CSCs, exploring whether the ALA-PDT mediated CSCs and invasion capabilities depending on EMT pathway will be investigated in the future. Chemotherapy is the current platform for treating HNC patients with metastasis; however, the chemotherapeutic effect is limited, and its side effects largely interfere with the quality of life of patients. CSCs are clinically characterized by resistance to chemotherapy. The presence of CSCs results in the low efficacy of anti-cancer therapies and the failure of tumor eradication and eventually leads to tumor recurrence and metastasis.