Arsenic is a well-documented environmental toxicant Epidemiological survey implicates that exposure to arsenic will induce neurotoxicity and peripheral vascular disease In fact arsenic trioxide (ATO) has also been used for medicinal purposes originally to treat acute promyelocytic leukemia (APL) showing ability for anticancer treatment Oral cancer has been in top 10 common cancers for decades in Taiwan and the incidence rate still increases year after year Around 75 percent of oral cancers are linked to modifiable behaviors such as tobacco use and excessive alcohol consumption Also betel chewing in some certain areas especially in Southeast Asia is known to be a strong risk factor for developing oral cancers In the present study we investigated three oral squamous carcinoma cells (Fadu OEC-M1 and OC3) treated by sodium arsenite (NaAsO2) and dimethylarsenic acid (DMA) to determine whether the arsenic compounds could be the anti-cancer agents Results showed that cells appeared rounded up and became membrane blebbing after treatments with NaAsO2 (1 μM) and DMA (1 mM) for 24 hr in OEC-M1 and OC3 cell lines and NaAsO2 (10 μM) and DMA (1 mM) for 24 hr in Fadu cell line respectively These morphological changes revealed characteristics of apoptosis In cell viability test the surviving percentage of all three cell lines significantly decreased as the dosage of arsenic compounds increased (10 to 100 μM NaAsO2 and 1 to 100 mM DMA) The impact of arsenic compounds on cell cycle regulation was detected by flow cytometry and data showed that the percentage of subG1 and G2/M phase cells among three cell lines increased in both NaAsO2 and DMA treatments We further confirmed that cells underwent apoptosis under both arsenic compound treatments through annexinV/PI double staining In addition examined by western blot activation of caspase-8 -9 and -3; cleavage of poly ADP-ribose polymerase (PARP); and phosphorylation of JNK ERK1/2 and p38 could all be observed by NaAsO2 and DMA treatments among three cell lines Taken together NaAsO2 and DMA could induce cell apoptosis through extrinsic and intrinsic apoptotic pathways and cause the activation of MAPK pathways in Fadu OEC-M1 and OC3 oral cancer cell lines
Anticancer Effect of Arsenic Compounds on Apoptosis in Oral Cavity Cancer Cells
巧雲, 朱. (Author). 2014 8月 21
學生論文: Master's Thesis