Hyaluronic Acid Triggers Human Acute Myeloid Leukemia Cell Death through an Apoptotic Pathway

• Main Authors: Chia, Chi-Hao, 賈繼皓
• Other Authors: Wu, Li-Chen
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/71995448250608419454

碩士 === 國立暨南國際大學 === 應用化學系 === 103 === Leukemia is a group of cancers that usually begins in the bone marrow and results in high numbers of abnormal white blood cells. Acute myeloid leukemia (AML) is the most common acute leukemia affecting adults, and its incidence increases with age. The current clinical treatment is still primarily on chemotherapy and bone marrow transplantation, but the 5-year survival rate is about 30 %. Thus, development of new therapeutics is urgently needed. Hyaluronic acid (HA), an extracellular matrix polyglycan, has been reported to have several biological functions, including immune system modulation and anti-inflammatory activity. However, the action of hyaluronic acid on human cancer cells is still controversial. To elucidate the effect of both normal HA and our special prepared HA（S-HA）and their molecular mechanism on human acute myeloid leukemia (AML), HL60 and KG-1 cell lines were used. Treatment with various concentrations of HA and S-HA for 48h, a significant cell death was observed in response to S-HA treatment. Flow cytometric analysis and Annexin V /Propidium iodide doubling staining showed that S-HA induced apoptotic cell death in treated human AML cell lines. Additionally, S-HA stimulated the activation of caspase-2, -3, -8 and -9. Moreover, S-HA not only enhanced the expression levels of pro-apoptotic proteins Bax and Bak, but also upregulated the death receptor Fas and DR5. Furthermore, S-HA decreased the anti-apoptotic protein Mcl-1 level. These results revealed that S-HA-triggered AML cell death through both extrinsic and intrinsic apoptotic pathway. Besides, data from human phospho-kinase array indicated that signaling pathway related protein STAT-2, -3 and -5 were reduced by S-HA, suggesting that STAT family molecular might be involved in S-HA-triggered AML cell apoptosis.