18P - Dehydroandrographolide, an iNOS inhibitor, extracted from from Andrographis paniculata (Burm.f.) Nees, induces autophagy in human oral cancer cells

Date 19 December 2015
Event ESMO Asia 2015 Congress
Session Poster presentation 1
Topics Basic Science
Presenter Mu-Kuan Chen
Citation Annals of Oncology (2015) 26 (suppl_9): 1-7. 10.1093/annonc/mdv517
Authors M. Chen
  • Department Of Otorhinolaryngology-head And Neck Surgery, Changhua Christian Hospital Cancer Research Center, 500 - Changhua City/TW

Abstract

Aim/Background

Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer and has a poor prognosis and low survival rate. Chemotherapy is the suggested treatment for advanced-stage cancers. Increasing focus is on providing a scientific basis for using these agents as a preventive strategy for people with a high risk of cancer. Autophagy, which is constitutively executed at the basal level in all cells, promotes cellular homeostasis by regulating the turnover of organelles and proteins. Several lines of indirect evidence indicate that autophagy acts as a mechanism for tumor suppression. Andrographis paniculata plant extract exhibits various pharmacological activities. Andrographolide, the major constituent of the extract, is implicated in its pharmacological activity. However, the pharmacological activities of dehydroandrographolide (DA) remain unclear.

Methods

In this study, we demonstrated that DA induces oral cancer cell viability and related molecular mechanism by MTT assay, annexin-V assay and Western bloting.

Results

DA significantly increased LC3-II and acidic vesicular organelle expression in oral cancer cells. Treatment with autophagy inhibitors inhibited DA-induced human oral cancer cell death. However, DA failed to reduce cell viability in the presence of the VZV-G pseudotyped lentivirus–shRNA system or siRNA knockdown autophagy-related gene, LC3 or beclin-1. Conversely, treatment with autophagy enhancers increased DA-induced cell death.

Conclusions

DA-induced autophagy was triggered by the activation of JNK1/2 and inhibition of Akt and p38. In conclusion, this study demonstrated that DA induced autophagy in human oral cancer cells by activating JNK1/2, and inhibiting Akt and p38. 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.

Clinical trial identification

N/A

Disclosure

All authors have declared no conflicts of interest.