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Oncology Commons

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Full-Text Articles in Oncology

Bh3 Mimetic Abt-737 Sensitizes Colorectal Cancer Cells To Ixazomib Through Mcl-1 Downregulation And Autophagy Inhibition., Lifeng Yang, Juefeng Wan, Sheng Xiao, Darryll Barkhouse, Ji Zhu, Guichao Li, Bo Lu, Zhen Zhang Jun 2016

Bh3 Mimetic Abt-737 Sensitizes Colorectal Cancer Cells To Ixazomib Through Mcl-1 Downregulation And Autophagy Inhibition., Lifeng Yang, Juefeng Wan, Sheng Xiao, Darryll Barkhouse, Ji Zhu, Guichao Li, Bo Lu, Zhen Zhang

Department of Radiation Oncology Faculty Papers

The proteasome inhibitor MLN9708 is an orally administered drug that is hydrolyzed into its active form, MLN2238 (ixazomib). Compared with Bortezomib, MLN2238 has a shorter proteasome dissociation half-life and a lower incidence and severity of peripheral neuropathy, which makes it an attractive candidate for colorectal cancer treatment. In the present study, we observed that MLN2238 induced autophagy, as evidenced by conversion of the autophagosomal marker LC3 from LC3I to LC3II, in colorectal cancer cell lines. Mcl-1, an anti-apoptotic Bcl-2 family protein, was markedly elevated after treating a colorectal cancer cell line with MLN2238. We proved that inhibiting Mcl-1 expression enhances …


Investigating The Use Of Chloroquine As Antineoplastic Therapy, Catherine E. Herron, Alexandra E. Mason May 2016

Investigating The Use Of Chloroquine As Antineoplastic Therapy, Catherine E. Herron, Alexandra E. Mason

Senior Honors Projects, 2010-2019

Chloroquine (CQ) is an oral lysosomotropic agent routinely used as an anti-malarial drug (Espina & Liotta, 2013). In recent years, it has been discovered that CQ also possesses anticancer effects, potentially due to the drug’s inhibition of autophagy (Kimura, Takabatake, Takahashi, & Isaka, 2012). Autophagy is a normal cellular pathway that allows for the degradation of cytoplasmic contents. In cancer cells autophagy can also serve as a pro-survival pathway under stressful metabolic conditions, ultimately promoting the survival of malignant cells (Sui et al., 2013). Therefore, in recent years CQ has been speculated as a potential antineoplastic therapy. When administered in …


Tumor Suppressor Spred2 Interaction With Lc3 Promotes Autophagosome Maturation And Induces Autophagy-Dependent Cell Death, Ke Jiang, Min Liu, Guibin Lin, Beibei Mao, Wei Cheng, Han Liu, Jozsef Gal, Haining Zhu, Zengqiang Yuan, Wuguo Deng, Quentin Liu, Peng Gong, Xiaolin Bi, Songshu Meng Mar 2016

Tumor Suppressor Spred2 Interaction With Lc3 Promotes Autophagosome Maturation And Induces Autophagy-Dependent Cell Death, Ke Jiang, Min Liu, Guibin Lin, Beibei Mao, Wei Cheng, Han Liu, Jozsef Gal, Haining Zhu, Zengqiang Yuan, Wuguo Deng, Quentin Liu, Peng Gong, Xiaolin Bi, Songshu Meng

Molecular and Cellular Biochemistry Faculty Publications

The tumor suppressor Spred2 (Sprouty-related EVH1 domain-2) induces cell death in a variety of cancers. However, the underlying mechanism remains to be elucidated. Here we show that Spred2 induces caspase-independent but autophagy-dependent cell death in human cervical carcinoma HeLa and lung cancer A549 cells. We demonstrate that ectopic Spred2 increased both the conversion of microtubule-associated protein 1 light chain 3 (LC3), GFP-LC3 puncta formation and p62/SQSTM1 degradation in A549 and HeLa cells. Conversely, knockdown of Spred2 in tumor cells inhibited upregulation of autophagosome maturation induced by the autophagy inducer Rapamycin, which could be reversed by the rescue Spred2. These data …


Novel Therapeutic Approaches To Induce Autophagy In Brain Cancer, Gillian Conway Jan 2016

Novel Therapeutic Approaches To Induce Autophagy In Brain Cancer, Gillian Conway

Doctoral

Glioblastoma Multiforme (GBM) is classified as a malignant grade IV astrocytoma, and is considered to be the most biologically aggressive brain tumour with a 5-year survival rate of ~4%. The most frequent issue arising with GBM tumours is the high level of resistance observed to conventional therapeutic methods i.e. surgery, chemotherapy and radiation, thus signifying the urgency for the development of novel therapeutic methods. This study aims to investigate and develop both a complimentary and novel method to overcome the current treatment barriers. We have investigated the use of novel technologies such as cold atmospheric plasma (CAP) as an alternative …