Glycolysis, Warburg effect & Cancer: Role of thiols

Topic 250 WORDS: Glycolysis, Warburg effect & Cancer: Role of thiols?

This week you learned about glycolysis and the chemical reactions and enzymes involved in this important metabolic pathway. You further learned that glyceraldehyde phosphate dehydrogenase (GAPDH) enzyme is not only an important key regulatory enzyme of glycolysis, but also recognized as a “moonshining” enzyme. GAPDH is also long known as an enzyme that is prone to inhibition by many toxins, e.g., Pertussis toxin, alkylating agents and many thiol compounds. You also heard about the Warburg effect in connection with glycolysis.

As you work on this week’s discussion board assignment, consider the following: 

• Cervical      cancer is the second highest number of deaths in female cancers, exceeded      only by breast cancer. This cancer carries high risks of morbidity and mortality      amongst women.
• Most      cervical cancers cells show abnormally high glycolysis rates.
• The      current standard of care for locally advanced cervical cancer is      concurrent cisplatin chemotherapy with pelvic irradiation.
• Despite      significant advances in radiation treatment delivery, more than 30% of      patients fail this treatment.

This week:

• Please      read this scientific article: Rashmi R., Huang X.      et al. Radio-resistant cervical cancers are sensitive to inhibition of      glycolysis and redox metabolism. Cancer Res. 2018 March 15; 78(6):      1392–1403.
• Do some      research on NCBI Pubmed (www.ncbi.nlm.nih.gov/pubmed) on      this week’s topic.
• Then discuss the following aspects      with your classmates:
  1. What       is the Warburg effect? How is it connected to glycolysis?
  2. What       are some of the reported metabolic characteristics of cervical cancer       cells?
  3. What       do scientists consider important thiols which may be responsible for the       resistance of cervical cancer cells to radio and brachytherapy?
  4. Why       and how do increased thiol levels confer increased resistance to radio-       and brachytherapy? And how can thiol levels be manipulated?
  5. Which       glycolysis enzyme is the most likely target candidate for thiol therapy?       Why?