Poster Presentation 30th Lorne Cancer Conference 2018

Investigating cellular responses in blood cancers when targeting the thioredoxin system with a gold compound (#279)

Sicong Wang 1 2 , Jun Hui Sze 1 2 , Yaoying Liu 1 2 , Yali Zhang 1 2 , Kyra Woods 1 , Giovanna Di Trapani 1 , Kathryn Tonissen 1 2
  1. School of Natural Sciences, Griffith University, Nathan, QLD, Australia
  2. Griffith Institute for Drug Discovery, Griffith University, Nathan, QLD, Australia

Lymphoma is a blood cancer raised from lymphocytes, which can be divided into Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). Lymphoma is expected to be the 6th most diagnosed cancer in Australia in 2017. Chronic myeloid leukaemia (CML) is another blood cancer and is a myeloproliferative disorder. Although many chemotherapies have been developed for the treatment of these blood cancers, they are still hard to cure and drug resistance often occurs. Drug resistance is induced by prolonged chemotherapy and by cells residing in a hypoxic environment. Lymphoma and CML cells can survive in the bone marrow, which is a hypoxic environment.

Recent studies showed that antioxidant systems play a key role in balancing the redox state in cells. CML and lymphoma have developed a capability to escape oxidative stress by upregulating the expression level of various cellular antioxidants, including the thioredoxin system. Moreover, the overexpression of the thioredoxin antioxidant system is associated with drug resistance and anti-apoptosis and the regulation of cellular signalling pathways such as the NF-κB and Nrf2 pathways. Therefore, targeting the thioredoxin system may be an effective approach to treat these blood cancers.

The gold compound Au-SBP (Au(d2pype)2)Cl) has been shown to inhibit the thioredoxin system in some cancer cells. However, the effectiveness of Au-SBP in blood cancers is not known. We have shown that Au-SBP can inhibit the growth of lymphoma and CML cell lines grown in both normoxia (20% oxygen) and hypoxia (1% oxygen). Thioredoxin reductase activity is also inhibited in cells treated with Au-SBP. This study is currently assessing the downstream cellular effects of treating cancer cells with this compound. Chromatin immunoprecipitation assays and qRT-PCR are being used to assess if the activity of the Nrf-2 and NF-κB transcription factors is altered in cells treated with this compound.