bafilomycin-a1 and Mouth-Neoplasms

Extensive research supports the administration of herbal medicines or natural foods during cancer therapy. Pterostilbene, a naturally occurring phytoalexin, has various pharmacological activities, including antioxidant activity, cancer prevention activity, and cytotoxicity to many cancers. However, the effect of pterostilbene on the autophagy of tumor cells has not been clarified.. In this study, the unique effects of pterostilbene on the autophagy of human oral cancer cells were investigated.. The results of this study showed that pterostilbene effectively inhibited the growth of human oral cancer cells by inducing cell cycle arrest and apoptosis. In addition, the formation of acidic vesicular organelles and LC3-II production also demonstrated that pterostilbene induced autophagy. Administering 3-methylamphetamine (3-MA) and bafilomycin A1 (BafA1) exerted differing effects on the pterostilbene-induced death of human oral cancer cells. Pterostilbene-induced autophagy was triggered by activation of JNK1/2 and inhibition of Akt, ERK1/2, and p38.. In conclusion, this study demonstrated that pterostilbene caused autophagy and apoptosis in human oral cancer cells, suggesting that pterostilbene could serve as a new and promising agent for treating human oral cancer.

Topics: Amphetamines; Apoptosis; Autophagy; Cell Cycle Checkpoints; Enzyme Inhibitors; Humans; Macrolides; MAP Kinase Signaling System; Microtubule-Associated Proteins; Mitogen-Activated Protein Kinases; Mouth Neoplasms; Organelles; Proto-Oncogene Proteins c-akt; Stilbenes

Numerous studies have demonstrated that autophagy is associated with cancer development. Thus, agents to induce autophagy could be employed in some cases for the treatment of cancer. Our results showed that tetrandrine significantly decreased the viability of SAS cells in a concentration- and time-dependent manner. Tetrandrine induced nuclear condensation, demonstrated by DAPI staining. The early events in apoptosis analysed by Annexin V/PI staining indicated that the percentage of cells staining positive for Annexin V was slightly increased in SAS cells with tetrandrine treatment but was much lower following bafilomycin A1 pre-treatment. Tetrandrine caused AVO and MDC induction in SAS cells in a concentration-dependent manner by fluorescence microscopy. Tetrandrine also caused LC-3 expression in SAS cells in a time-dependent manner. Our results show that tetrandrine treatment induced the levels of cleaved caspase-3 in a concentration- and time-dependent manner. Tetrandrine treatment induced the levels of LC-3 II, Atg-5, beclin-1, p-S6, p-ULK, p-mTOR, p-Akt (S473) and raptor. Tetrandrine decreased cell viability, but bafilomycin A1, 3-MA, chloroquine and NAC protected tetrandrine-treated SAS cells against decrease of cell viability. Atg-5, beclin-1 siRNA decreased tetrandrine-induced cleaved caspase-3 and cleaved PARP in SAS cells and protected tetrandrine-treated SAS cells against decrease in cell viability. Chloroquine, NAC and bafilomycin A1 also decreased tetrandrine-induced cleaved caspase-3 and cleaved PARP in SAS cells. Our results indicate the tetrandrine induces apoptosis and autophagy of SAS human cancer cells via caspase-dependent and LC3-I and LC3-II‑dependent pathways.

Topics: Antineoplastic Agents, Phytogenic; Antirheumatic Agents; Apoptosis; Apoptosis Regulatory Proteins; Autophagy; Autophagy-Related Protein-1 Homolog; Beclin-1; Benzylisoquinolines; Carcinoma, Squamous Cell; Caspase 3; Cell Line, Tumor; Cell Survival; Chloroquine; Enzyme Inhibitors; Humans; Intracellular Signaling Peptides and Proteins; Macrolides; Membrane Proteins; Microtubule-Associated Proteins; Mouth Neoplasms; Poly(ADP-ribose) Polymerases; Protein Serine-Threonine Kinases; RNA Interference; RNA, Small Interfering