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conferenceseries
.com
Volume 10
Journal of Cancer Science & Therapy
Oncologists 2018
May 24-25, 2018
May 24-25, 2018 Osaka, Japan
22
nd
Global Annual Oncologists Meeting
Metabolic targeting of glioblastoma cells
P Sinha
1,
3
, S Lawler
2
and P Chumas
3
1
Royal Hallamshire Hospital, UK
2
Brigham and Women’s Hospital, USA
3
Leeds Teaching Hospitals NHS Trust, UK
B
rain tumor account for less than 2% of all primary cancers; however still 1860 new cases of malignant gliomas are diagnosed
each year in England and Wales. Standard care of treatment for patients with glioblastoma is surgery followed by adjuvant
radiotherapy and chemotherapy. However, glioblastoma is a highly aggressive and infiltrating tumor and in spite of advances
in radiotherapy, chemotherapy and surgical technique, there has not been significant improvement in patient survival. As
cure for GBM remain elusive, it is important to identify new treatment modalities as well as modify existing therapies to
possibly change malignant gliomas from a deadly disease into a chronic one. In this study, we initially investigated the effect
of glucose deprivation on adult glioma cell viability. We have shown that glucose deprivation induced glioma cell death in
vitro. We have also shown that free radical scavenger N-acetylcysteine and methyl pyruvate suppressed glucose deprivation
induced cell death. We have shown that glucose deprivation induced cell death is not mediated by apoptosis, autophagy or
necrosis. Glucose deprivation led to energetic and endoplasmic reticulum (ER) stress in glioma cells. We have also shown that
hypoxia rescued glucose deprivation induced cell death whereas glutamine withdrawal had no effect on glucose deprivation
induced cell death. We have shown that glucose deprivation and hypoxia promotes glioma cell migration. We then showed that
metformin significantly enhanced glucose deprivation induced cell death which was not mediated by apoptosis, autophagy,
necrosis or oxidative stress. We have also shown that AMPK mimic AICAR also promoted glucose deprivation induced cell
death whereas 2-deoxyglucose (2DG) suppressed glucose deprivation induced cell death. We have also shown that metformin
potentiated glucose deprivation induced energetic stress whereas it suppressed ER chaperone protein GRP78. We have shown
that metformin and 2DG combination led to significant cell death in glioma cells which were caspase independent and not
mediated by oxidative stress. Finally we have also showed that metformin potentiated 2DG mediated pAMPK up-regulation
whereas it down-regulated 2DG mediated autophagy and ER chaperone protein GRP78 to induce cell death.
priyanksinha@me.comJ Cancer Sci Ther 2018, Volume 10
DOI: 10.4172/1948-5956-C3-130