dehydroandrographolide and Mouth-Neoplasms

Oral cancer is a type of head and neck cancer that is characterized by cancerous tissue growth in the oral cavity. Andrographolide and dehydroandrographolide (DA) are the two principal components of Andrographis paniculata (Burm.f.) Nees and are the main contributors to its therapeutic properties. However, the pharmacological activities of DA remain unclear.. In this study, we used wound closure assay and Boyden chamber assay to determine the effects of DA on oral cancer cell migration and invasion.. DA treatment significantly inhibited the migration and invasion abilities of SCC9 cells in vitro. Gelatin zymography and Western blotting results revealed that DA inhibited MMP-2 activity and reduced its protein levels. DA inhibited the phosphorylation of ERK1/2, p38, and JNK 1/2 in SCC9 cells. According to the mRNA levels detected using real-time PCR, DA inhibited MMP-2 expression in SCC9 cells. This inhibitory effect was associated with the upregulation of the TIMP-2 and downregulation of NF-κB, AP-1, and SP-1 expression. In addition, DA suppressed carcinoma-associated epithelial-mesenchymal transition in SCC9 cells. Finally, DA administration effectively suppressed MMP-2 expression and tumor metastases in the oral carcinoma xenograft mouse model in vivo.. DA inhibits the invasion of human oral cancer cells and is a potential chemopreventive agent against oral cancer metastasis.

Topics: Animals; Cell Line, Tumor; Diterpenes; Humans; Male; Matrix Metalloproteinase 2; Mice; Mice, Inbred BALB C; Mouth Neoplasms; Neoplasm Metastasis; NF-kappa B; Protease Inhibitors; Sp1 Transcription Factor; Transcription Factor AP-1

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.

Topics: AMP-Activated Protein Kinases; Andrographis; Animals; Antineoplastic Agents, Phytogenic; Autophagy; Cell Line, Tumor; Diterpenes; Dose-Response Relationship, Drug; Enzyme Inhibitors; Humans; JNK Mitogen-Activated Protein Kinases; Male; Mice, Inbred BALB C; Mice, Nude; Microtubule-Associated Proteins; Mouth Neoplasms; Nitric Oxide Synthase Type II; p38 Mitogen-Activated Protein Kinases; Phytotherapy; Plant Extracts; Plants, Medicinal; Proto-Oncogene Proteins c-akt; RNA Interference; Signal Transduction; Time Factors; TOR Serine-Threonine Kinases; Transfection; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays