Curcumin Analog L48H37 Induces Apoptosis in Human Oral Cancer Cells by Activating Caspase Cascades and Downregulating the Inhibitor of Apoptosis Proteins through JNK/p38 Signaling.

L48H37 is a synthetic curcumin analog that has anticancer potentials. Here, we further explored the anticancer effect of L48H37 on oral cancer cells and its mechanistic acts. Cell cycle distribution was assessed using flow cytometric analysis. Apoptosis was elucidated by staining with PI/Annexin V and activation of the caspase cascade. Cellular signaling was explored using apoptotic protein profiling, Western blotting, and specific inhibitors. Our findings showed that L48H37 significantly reduced the cell viability of SCC-9 and HSC-3 cells, resulting in sub-G1 phase accumulation and increased apoptotic cells. Apoptotic protein profiling revealed that L48H37 increased cleaved caspase-3, and downregulated cellular inhibitor of apoptosis protein 1 (cIAP1) and X-linked inhibitor of apoptosis protein (XIAP) in SCC-9 cells, and the downregulated cIAP1 and XIAP in both oral cancer cells were also demonstrated by Western blotting. Meanwhile, L48H37 triggered the activation of caspases and mitogen-activated protein kinases (MAPKs). The involvement of c-Jun N-terminal kinase (JNK) and p38 MAPK (p38) in the L48H37-triggered apoptotic cascade in oral cancer cells was also elucidated by specific inhibitors. Collectively, these findings indicate that L48H37 has potent anticancer activity against oral cancer cells, which may be attributed to JNK/p38-mediated caspase activation and the resulting apoptosis. This suggests a potential benefit for L48H37 for the treatment of oral cancer.

Curcumin and its Analogs and Carriers: Potential Therapeutic Strategies for Human Osteosarcoma.

Curcumin is a natural polyphenol phytochemical derived from turmeric with antioxidant, anti-inflammatory, and anticancer properties but is concerned about poor solubility in water, absorption, and metabolic stability. Potent metastatic osteosarcoma is the most common primary bone cancer in children, adolescents, and young adults. It is responsible for low survival rates because of its high rate of metastasis to the lungs. To improve poor bioavailability, numerous curcumin analogs were developed to possess anticancer characteristics through a variety of biological pathways involved in cytotoxicity, proliferation, autophagy, sensitizing chemotherapy, and metastases. This review provides an overview of their various pharmacological functions, molecular mechanisms, and therapeutic potential as a remedy for human osteosarcoma. To enhance therapeutic efficacy, several liposomal nanoparticles, nanocarriers, multifunctional micelles, and three-dimensional printed scaffolds have also been developed for the controlled delivery of curcumin targeting human osteosarcoma cells. Consequently, curcumin and several potential analogs and delivery formulations are optimistic candidates to improve the currently available strategy for human osteosarcoma. However, further insight into the mechanism of action of promising curcumin analogs and the development of carriers in clinical trials of osteosarcoma needs to be investigated to improve their overall potency and clinical utility, in particular the anti-metastatic effect.

Gambogic Acid Induces HO-1 Expression and Cell Apoptosis through p38 Signaling in Oral Squamous Cell Carcinoma.

Gambogic acid (GA), a natural and bioactive compound from the gamboge resin, has been reported to exhibit many oncostatic activities against several types of malignancies. However, its effects on the progression of oral squamous cell carcinoma (OSCC) remain largely unexplored. To fill this gap, we investigated the anticancer role of GA and molecular mechanisms underlying GA's actions in combating oral cancer. We found that GA negatively regulated the viability of OSCC cells, involving induction of the sub-G1 phase and cell apoptosis. In addition, a specific signature of apoptotic proteome, such as upregulation of heme oxygenase-1 (HO-1) and activation of caspase cascades, was identified in GA-treated OSCC. Moreover, such induction of HO-1 expression and caspase cleavage by GA was significantly diminished through the pharmacological inhibition of p38 kinase. In conclusion, these results demonstrate that GA promotes cell apoptosis in OSCC, accompanied with the activation of a p38-dependent apoptotic pathway. Our findings provide potential avenues for the use of GA with high safety and therapeutic implications in restraining oral cancer.

Magnolol Triggers Caspase-Mediated Apoptotic Cell Death in Human Oral Cancer Cells through JNK1/2 and p38 Pathways.

Magnolol is a natural compound extracted from Chinese herbal medicine and can induce apoptosis in numerous types of cancer cells. However, the molecular mechanisms of magnolol in oral cancer are still unclear. In this study, we investigated the anti-cancer effects and underlying mechanisms of magnolol in human oral cancer cell lines. Our results exhibited that magnolol inhibited the cell proliferation via inducing the sub-G1 phase and cell apoptosis of HSC-3 and SCC-9 cells. The human apoptosis array and Western blot assay showed that magnolol increased the expression of cleaved caspase-3 proteins and heme oxygenase-1 (HO-1). Moreover, we proved that magnolol induces apoptosis in oral cancer cell lines via the c-Jun N-terminal kinase (JNK)1/2 and p38 pathways. Overall, the current study supports the role for magnolol as a therapeutic approach for oral cancer through JNK1/2- and p38-mediated caspase activation.

Dihydromyricetin suppresses cell metastasis in human osteosarcoma through SP-1- and NF-κB-modulated urokinase plasminogen activator inhibition.

BACKGROUND: Metastasis caused a decline in the 5-years survival rate of osteosarcoma. Therefore, developing new targeted therapeutics for osteosarcoma treatment is imperative. Dihydromyricetin (DHM) has several physiological functions: it counteracts inflammation, oxidation, and antitumor properties. However, the effects of DHM on osteosarcoma and its underlying mechanisms are still not well understood. PURPOSE: In this study, we investigated the antimetastatic properties of DHM in human osteosarcoma U-2 OS and HOS cells. METHODS: The effects of DHM (0, 25, 50, 75, and 100 µM) on cell viability, migration, and invasion were examined. Western blotting, RT-PCR, and quantitative real-time PCR (QPCR) were determined urokinase plasminogen activator (uPA) expression. The expression of transcriptional factor SP-1 and NF-κB was determined by using immunofluorescence assay, chromatin immunoprecipitation assay, and site-directed mutagenesis luciferase reporter. RESULTS: We observed that DHM suppresses cell migration and invasion in osteosarcoma cell lines. In addition, DHM inhibits metastasis by downregulating urokinase plasminogen activator (uPA) expression. Moreover, real-time polymerase chain reaction and promoter activity assays revealed that DHM decreased uPA expression at transcription levels. Furthermore, the inhibition of uPA expression was associated with the suppression of SP-1 and NF-κB, which bind to the uPA promoter. Regardless of blocking or inducing the extracellular signal-regulated kinase (ERK) pathway, we verified that the DHM-related suppression of uPA and cell metastasis occurred through the p-ERK pathway. CONCLUSION: We are the first study to propose that DHM suppresses osteosarcoma metastasis through the ERK pathway and through the suppression of SP-1 and NF-κB to inhibit downstream uPA expression. DHM is a potential therapeutic agent for antimetastatic therapy against osteosarcoma.

Tricetin Suppresses Migration and Presenilin-1 Expression of Nasopharyngeal Carcinoma through Akt/GSK-3ß Pathway.

Lymph node migration results in poor prognoses for nasopharyngeal carcinoma (NPC) patients. Tricetin, a flavonoid derivative, regulates tumorigenesis activity through its antiproliferative and antimetastatic properties. However, the molecular mechanism of tricetin affecting the migration and invasion of NPC cells remains poorly understood. In this paper, we examined the antimetastatic properties of tricetin in human NPC cells. Our results demonstrated that tricetin at noncytotoxic concentrations (0-80 3M) noticeably reduced the migration and invasion of NPC cells (HONE-1, NPC-39, and NPC-BM). Moreover, tricetin suppressed the indicative protease, presenilin-1 (PS-1), as indicated by protease array. PS-1 was transcriptionally inhibited via the Akt signaling pathway but not mitogen-activated protein kinase pathways, such as the JNK, p38, and ERK1/2 pathways. In addition to upregulating GSK-3[Formula: see text] phosphorylation through Akt suppression, tricetin may downregulate the activity of PS-1. Overall, our study provides new insight into the role of tricetin-induced molecular regulation in the suppression of NPC metastasis and suggests that tricetin has prospective therapeutic applications for patients with NPC.

Dioscorea nipponica Makino suppresses TPA-induced migration and invasion through inhibition of matrix metalloproteinase-9 in human cervical cancer cells.

Dioscorea nipponica Makino has been used for the treatment of chronic bronchitis, rheumatoid arthritis, cough, and asthma. Several studies have established the antitumor effect of D. nipponica Makino extract (DNE). However, no investigations have considered the antimetastatic potential of DNE in cervical cancer cells. The present study examined the effects of DNE on cervical cancer cells treated with 12-O-tetradecanoylphorbol-13-acetate and characterized the possible molecular mechanisms. MTT assay results indicated that DNE exhibited very low cytotoxicity, and DNE significantly reduced the invasion and migration abilities of cervical cancer cells. Gelatin zymography analysis revealed that DNE significantly inhibited matrix metalloproteinase-9 (MMP-9) activity. Reverse transcription-polymerase chain reaction assay results revealed that DNE treatment inhibited the MMP-9 mRNA levels of HeLa and SiHa cells. Western blot results revealed that DNE significantly diminished the ERK1/2 phosphorylation. In conclusion, we revealed that the antimetastatic effects of DNE on cervical cancer cells are due to its inhibition of MMP-9 expression through the ERK1/2 pathway.

New insights into antimetastatic signaling pathways of melatonin in skeletomuscular sarcoma of childhood and adolescence.

Melatonin is an indole produced by the pineal gland at night under normal light or dark conditions, and its levels, which are higher in children than in adults, begin to decrease prior to the onset of puberty and continue to decline thereafter. Apart from circadian regulatory actions, melatonin has significant apoptotic, angiogenic, oncostatic, and antiproliferative effects on various cancer cells. Particularly, the ability of melatonin to inhibit skeletomuscular sarcoma, which most commonly affects children, teenagers, and young adults, is substantial. In the past few decades, the vast majority of references have focused on the concept of epithelial-mesenchymal transition involvement in invasion and migration to allow carcinoma cells to dissociate from each other and to degrade the extracellular matrix. Recently, researchers have applied this idea to sarcoma cells of mesenchymal origin, e.g., osteosarcoma and Ewing sarcoma, with their ability to initiate the invasion-metastasis cascade. Similarly, interest of the effects of melatonin has shifted from carcinomas to sarcomas. Herein, in this state-of-the-art review, we compiled the knowledge related to the molecular mechanism of antimetastatic actions of melatonin on skeletomuscular sarcoma as in childhood and during adolescence. Utilization of melatonin as an adjuvant with chemotherapeutic drugs for synergy and fortification of the antimetastatic effects for the reinforcement of therapeutic actions are considered.

Salvianolic acid A suppresses MMP-2 expression and restrains cancer cell invasion through ERK signaling in human nasopharyngeal carcinoma.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge, as known as Danshen, has used for the prevention and treatment of cardiovascular diseases clinically and anti-cancer activities. Salvianolic acid A (SAA), one of the most abundant ingredients, hydrophilic derivatives of Salvia miltiorrhiza Bunge, exerts a variety of pharmacological actions, such as anti-oxidative, anti-inflammatory and anti-cancer activities. However, the impact of SAA on nasopharyngeal carcinoma (NPC) invasion and metastasis remains unexplored. AIM OF THE STUDY: To investigate the potential of SAA to prevent migration and invasion on NPC cell. MATERIALS AND METHODS: MTT assay and Boyden chamber assay were performed to determine cell proliferation, migration and invasion abilities, respectively. The activity and protein expression of matrix metalloproteinase-2 (MMP-2) were determined by gelatin zymography and western blotting. RESULTS: Here, we showed that SAA considerably suppressed the migrative and invasive activity of human NPC cells but not rendered cytotoxicity. In SAA-treated NPC cells, the activity and expression of matrix metalloproteinase-2 (MMP-2), a key regulator of cancer cell invasion, were reduced. Additionally, the presence of high concentrations of SAA dramatically abolished the activation of focal adhesion kinase (FAK) and moderately inhibited the phosphorylation of Src and ERK in NPC cells. CONCLUSIONS: Our results demonstrated that SAA inhibited the migration and invasion of NPC cells, accompanied by downregulation of MMP-2 and inactivation of FAK, Src, and ERK pathways. These findings indicate a usefulness of SAA on restraining NPC invasion and metastasis.

Erianin Induces Apoptosis and Autophagy in Oral Squamous Cell Carcinoma Cells.

Oral squamous cell carcinoma (OSCC) is a leading cause of cancer-related deaths worldwide. It has a very poor prognosis with over a 5-year survival rate of only 50%. Thus, it is important to identify effective therapeutic interventions against oral cancer. Apoptosis and autophagy have reported genetically regulated in physiology and diseases, which close relationship. Many natural compound study objects anticancer effect have been studied between apoptosis and autophagy relationship. The present study was designed to evaluate the effect of erianin on human oral cancer cell proliferation. Results of the study revealed that treatment with erianin significantly reduced the viability of different OSCC cell lines. Erianin exerted its cytotoxic effect by inducing cell cycle arrest and caspase-dependent apoptotic pathways. Both intrinsic and extrinsic pathways were found to be involved in erianin-mediated cell death. In addition, treatment with erianin also increased autophagy in OSCC cells. With further analysis, it was found that erianin induced both apoptosis and autophagy by regulating MAPK signaling pathways. Taken together, our study indicates that erianin plays an important role in reducing oral cancer cell viability, and thus, can be considered as a potential anticancer agent.

Duchesnea indica extract attenuates oral cancer cells metastatic potential through the inhibition of the matrix metalloproteinase-2 activity by down-regulating the MEK/ERK pathway.

BACKGROUND: Duchesnea indica (Andr.) Focke, an herb in folk medicine used extensively in traditional Chinese medicine, has cytostatic properties as well as antioxidant and antimetastasis activities in various cancer cells. However, the effects and underlying mechanisms of Duchesnea indica extracts (DIEs) on human oral squamous cell carcinoma (OSCC) metastases remain unclear. PURPOSE: In this study, we posit the hypothesis that DIE possesses antimetastatic effects on human OSCC cells. METHODS: The effects of DIE on cell viability, motility, migration, and invasion were investigated. Gelatin zymography, Western blotting, migration and invasion assays were used to further study the underlying mechanisms involved in the antimetastatic effects of DIE in OSCC cells. RESULTS: The results from MTT assay revealed that DIE did not affect the cell viability of OSCC cells. Moreover, DIE significantly attenuated OSCC cells' motility, migration, and invasion by reducing the MMP-2 protein expression and MMP-2 activity in a dose-dependent manner. In addition, DIE reduced the phosphorylation of both ERK1/2 and its upstream kinase but had no effect on the phosphorylation of p38 and JNK. CONCLUSION: DIE triggers the antimetastatic activity in OSCC cells by suppressing the MMP-2 activity via the MEK/ERK signaling pathways. Therefore, these findings are promising for the use of DIE antimetastatic activity in oral cancer metastasis treatment.

The Potential of Chinese Herbal Medicines in the Treatment of Cervical Cancer.

Cervical cancer is a global health issue and places a considerable economic and medical burden on society. Thus, a concerted effort to improve the treatment of cervical cancer is warranted. Although several treatment options are currently available for treating patients with cervical cancer, such as chemoradiation and neoadjuvant or adjuvant chemotherapy, more aggressive systemic therapies and newer therapeutic agents are under investigation. Medicinal herbs have long been used to treat diseases. In this review, we summarize studies analyzing the antitumor effects and underlying mechanisms of Chinese herbal medicines, including the effects of crude extracts and compounds in vitro or in animal models for inducing apoptosis and inhibiting invasion or metastasis. Chinese herbal medicines with therapeutic targeting, such as those that interfere with tumor growth and progression in cervical cancer, have been widely investigated. To apply Chinese herbal medicine in the treatment of cervical cancer, adequate clinical studies are required to confirm its clinical safety and efficiency. Further investigations focused on the purification, pharmacokinetics, and identification of compounds from Chinese herbal medicines in cervical cancer treatment are necessary to achieve the aforementioned treatment goals.

Geraniin inhibits oral cancer cell migration by suppressing matrix metalloproteinase-2 activation through the FAK/Src and ERK pathways.

Geraniin has been reported to have numerous biological activities, including antiviral, antihypertensive, antihyperglycaemic, liver protective, antidiabetic, and apoptotic activities. However, the anti-migration effects of geraniin on oral cancer remain elusive. In this study, we revealed the potential antitumor mechanisms of geraniin through the inhibition of the migration and invasion of human oral cancer cell lines SCC-9 and SCC-14. The results of gelatin zymography and Western blot assays revealed that geraniin significantly reduced the activity and expression of matrix metalloproteinase-2 (MMP-2) of oral cancer cells in a concentration-dependent manner. Furthermore, geraniin potently suppressed the phosphorylation of focal adhesion kinase (FAK), Src, and extracellular signal-regulated kinase (ERK)1/2 but did not affect the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase 1/2. Moreover, blocking the MAPK/ERK1/2 pathway significantly enhanced the anti-migration ability of geraniin in oral cancer cells. In conclusion, we demonstrated that geraniin inhibits the motility of SCC-9 and SCC-14 cells in vitro through a molecular mechanism that involves the attenuation of MMP-2 expression and activity mediated by decreased FAK/Src and ERK1/2 pathways.

Antimetastatic effects of Eclipta prostrata extract on oral cancer cells.

Eclipta prostrata, a traditional Chinese medication, has been used for the treatment of several diseases. However, the molecular mechanism underlying the effects of Eclipta prostrata extracts (EPE) on human oral cancer cell metastasis remains unclear. We thus examined the effects of EPE on metastasis promoting proteins in oral cancer. Our results revealed that the EPE attenuated SCC-9, HSC-3, and TW2.6 cell migration and invasiveness by reducing matrix metalloproteinase (MMP)-2 enzyme activities. In addition, Western blot analysis revealed that EPE significantly reduced the levels of phosphorylated extracellular signal-regulated kinase 1/2 (ERK 1/2) but not those of c-Jun N-terminal kinase (JNK) 1/2 and p38. In conclusion, we found that EPE could inhibit oral cancer metastasis through the inhibition of MMP-2 expression. Therefore, EPE may be used to prevent the metastasis of oral cancer, and has the potential to be applied to cancer treatment.

Rubus idaeus Inhibits Migration and Invasion of Human Nasopharyngeal Carcinoma Cells by Suppression of MMP-2 through Modulation of the ERK1/2 Pathway.

Nasopharyngeal carcinoma (NPC) is characterized by a high incidence of metastasis in the neck lymph nodes, resulting in a poor prognosis and posing challenges for treatment. In this study, we investigated the in vitro antimetastatic properties of Rubus idaeus extract (RIE) on human nasopharyngeal carcinoma cells. HONE-1, NPC-39 and NPC-BM cells were subjected to RIE treatment, and effects on the migration and invasion of tumor cells were analyzed. The results showed that RIE suppressed the migration and invasion of NPC cells. Gelatin zymography assay, Western blotting and real-time PCR showed that matrix metalloproteinases-2 (MMP-2) enzyme activity, protein expression and mRNA levels were down-regulated by RIE treatment. To identify the signaling pathway, mitogen-activated protein kinase proteins were examined, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of RIE. In summary, our data showed that RIE inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by down-regulating the ERK1/2 signaling pathway, suggesting that Rubus idaeus may serve as chemotherapeutic and chemopreventive agent for NPC.

Antimetastatic effects of Rheum palmatum L. extract on oral cancer cells.

Rheum palmatum L., a traditional Chinese medication, has been used for the treatment of various disorders. However, the detailed impacts and underlying mechanisms of R. palmatum L. extracts (RLEs) on human oral cancer cell metastasis are still unclear. Here, we tested the hypothesis that an RLE has antimetastatic effects on SCC-9 and SAS human oral cancer cells. Gelatin zymography, Western blot, real-time polymerase chain reaction, and luciferase assay were used to explore the underlying mechanisms involved in the antimetastatic effects on oral cancer cells. Our results revealed that the RLE (up to 20 µg/mL, without cytotoxicity) attenuated SCC-9 and SAS cell motility, invasiveness, and migration by reducing matrix metalloproteinase (MMP)-2 enzyme activities. Western blot analysis of the MAPK signaling pathway indicated that the RLE significantly decreased phosphorylated ERK1/2 levels but not p38 and JNK levels. In conclusion, RLEs exhibit antimetastatic activity against oral cancer cells through the transcriptional repression of MMP-2 via the Erk1/2 signaling pathways. Thus, RLEs may be potentially useful as antimetastatic agents for oral cancer chemotherapy.

PG2, a botanically derived drug extracted from Astragalus membranaceus, promotes proliferation and immunosuppression of umbilical cord-derived mesenchymal stem cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus membranaceus is used to manage the deficiency of vital energy in traditional Chinese medicine and confirmed to have many biological functions. Mesenchymal stem cells (MSCs) possess immunosuppressive effects, and are widely used for regenerative medicine and immune disorders. AIMS OF STUDY: This study investigated the effects of Astragalus polysaccharides (APS) on umbilical cord-derived MSCs (UCMSCs), including morphology, surface marker expression, proliferation, differentiation, and in-vitro and in-vivo immunosuppressive capacities. MATERIALS AND METHODS: MSCs isolated from umbilical cords were used. PG2 injection, a botanically derived drug containing a mixture of APS, was added into the culture medium to prepare PG2-treated UCMSCs. The morphology, surface marker expression, proliferation, and differentiation of UCMSCs were determined. The in-vitro immunosuppressive effects of UCMSCs were examined by peripheral blood mononuclear cell (PBMC) proliferation assay. The in-vivo effects were evaluated by circulatory inflammation-associated cytokine levels in mice with septic peritonitis induced by cecal ligation and puncture (CLP) operation. RESULTS: Compared with control UCMSCs, UCMSCs had higher population doublings when exposed to PG2-containing medium (P = 0.003). The reduction rates of PBMC proliferation after phytohemagglutinin stimulation increased significantly when UCMSCs were treated with PG2 (P = 0.004). The serum levels of inflammation-associated cytokines, including TNF-α, IL-6, MCP-1, IFN-γ, and IL-1ß, were significantly lower at 6h after CLP in the mice receiving PG2-treated UCMSCs. CONCLUSIONS: Our results demonstrated that PG2 can enhance UCMSC proliferation and their in-vitro and in-vivo immunosuppressive effects. Consequently, UCMSCs can be obtained in earlier passages to avoid senescence, and sufficient cells can be acquired faster for clinical use. With stronger immunosuppressive effects, UCMSCs may treat immune disorders more effectively. Further studies are warranted.

Rubus idaeus extract suppresses migration and invasion of human oral cancer by inhibiting MMP-2 through modulation of the Erk1/2 signaling pathway.

Raspberries (Rubus idaeus L.) have been extensively studies worldwide because of their beneficial effects on health. Recently reports indicate that crude extracts of Rubus idaeus (RIE) have antioxidant and anticancer ability. The aim of this study was to evaluate the mechanism of its antimetastatic ability in oral cancer cells. In this study, SCC-9 and SAS oral cancer cells were subjected to a treatment with RIE and then analyzed the effect of RIE on migration and invasion. The addition of RIE inhibited the migration and invasion ability of oral cancer cells. Real time PCR, western blot and zymography analysis demonstrated that mRNA, protein expression and enzyme activity of matrix metalloproteinases-2 (MMP-2) were down-regulated by RIE. Moreover, the phosphorylation of Focal adhesion kinase (FAK), src, and extracellular signal-regulated kinase (ERK) were inhibited after RIE treatment. In conclusion, these results demonstrated that RIE exerted an inhibitory effect of migration and invasion in oral cancer cells and alter metastasis by suppression of MMP-2 expression through FAK/Scr/ERK signaling pathway. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1037-1046, 2017.

Corrigendum to "Caffeic Acid Phenethyl Ester Inhibits Oral Cancer Cell Metastasis by Regulating Matrix Metalloproteinase-2 and the Mitogen-Activated Protein Kinase Pathway".

[This corrects the article DOI: 10.1155/2012/732578.].

Dehydroandrographolide, an iNOS inhibitor, extracted from Andrographis paniculata (Burm.f.) Nees, induces autophagy in human oral cancer cells.

Autophagy, which is constitutively executed at the basal level in all cells, promotes cellular homeostasis by regulating the turnover of organelles and proteins. Andrographolide and dehydroandrographolide (DA) are the two principle components of Andrographis paniculata (Burm.f.) Nees. and are the main contributors to its therapeutic properties. However, the pharmacological activities of dehydroandrographolide (DA) remain unclear. In this study, DA induces oral cancer cell death by activating autophagy. Treatment with autophagy inhibitors inhibited DA-induced human oral cancer cell death. In addition, DA increased LC3-II expression and reduced p53 expression in a time- and concentration-dependent manner. Furthermore, DA induced autophagy and decreased cell viability through modulation of p53 expression. DA-induced autophagy was triggered by an activation of JNK1/2 and an inhibition of Akt and p38. In conclusion, this study demonstrated that DA induced autophagy in human oral cancer cells by modulating p53 expression, activating JNK1/2, and inhibiting Akt and p38. Finally, an administration of DA effectively suppressed the tumor formation in the oral carcinoma xenograft model in vivo. This is the first study to reveal the novel function of DA in activating autophagy, suggesting that DA could serve as a new and potential chemopreventive agent for treating human oral cancer.