生活習慣、飲食控制、環境因素等都有可能引起細胞代謝上的改變，且許多研究指出代謝的改變亦可能是造成癌症發生的原因之一，因此，近年來癌症代謝逐漸成為熱門的議題。攝護腺癌是男性中常見的癌症之一，根據衛生福利部在2018年的統計數據，攝護腺癌在台灣十大癌症死因中排名第六，病患接受治療後仍然有復發的可能性。咖啡酸苯乙酯 (caffeic acid phenethyl ester，CAPE)為蜂膠中的有效成分，具有抗菌、抗病毒、抗氧化、抗發炎、抗腫瘤以及抗癌等多種生物活性，本實驗室在先前的研究中已證實咖啡酸苯乙酯可以透過抑制攝護腺癌細胞中的Akt訊號傳遞來抑制癌細胞的生長與增生、活化非典型的Wnt訊息傳遞抑制攝護腺癌細胞的轉移與侵襲，但對於咖啡酸苯乙酯在癌症代謝方面尚未有研究。因此，本研究欲探討咖啡酸苯乙酯對於攝護腺癌細胞LNCaP C4-2B的代謝作用及影響，以評估咖啡酸苯乙酯是否能透過代謝重整降低癌細胞生長，達到癌症治療的效果。透過細胞增生及細胞活性試驗的結果顯示咖啡酸苯乙酯能夠抑制攝護腺癌細胞的生長，並利用海馬生物能量測定儀即時偵測細胞內的有氧呼吸及糖解作用，分析結果顯示低濃度的咖啡酸苯乙酯不只提升了癌細胞內粒線體的呼吸作用同時也促進糖解作用，推測咖啡酸苯乙酯可能會對癌細胞產生壓力使得細胞需要提升能量以維持細胞生存。我們也發現咖啡酸苯乙酯會降低癌細胞內的ROS，並提升AMPK的活化。我們的研究顯示，咖啡酸苯乙酯對攝護腺癌細胞的生長抑制可能部分是透過對癌細胞新陳代謝的影響。

There are many factors causing changes in cell metabolism, such as lifestyle habits, diet control, and environmental factors. Many studies indicate that altered metabolism may be one of the reasons for carcinogenesis. Thus, cancer metabolism has gradually become a hot topic in recent years. Prostate cancer (PCa) is one of the common cancers among men. According to the statistics of the Ministry of Health and Welfare in 2018, PCa is the sixth among the top ten causes of cancer death in Taiwan. Patients may still relapse after receiving treatment. Caffeic acid phenethyl ester (CAPE) is one of the main active ingredients in honey bee propolis and has various biological activities, such as antibacterial, antiviral, antioxidant, anti-inflammatory, anti-tumor, and anti-cancer. It has been reported by our lab previously that CAPE treatment suppresses proliferation of PCa cells by inhibiting Akt signaling pathway (Chuu et al., 2012) and inhibits the migration and invasion of PCa cells via activation of non-canonical Wnt signaling (Tseng et al., 2016). However, the effects of CAPE treatment on metabolism in PCa cells has not been studied. Therefore, this study intends to explore the effects of CAPE treatment on metabolism in PCa LNCaP C4-2B cells. The results of cell proliferation and cell survival assays revealed that CAPE inhibited the cell growth of PCa cells. We used the Seahorse XFe Analyzer to evaluate the effects of CAPE treatment on mitochondrial biofunction and glycolysis in LNCaP C4-2B cells. Low concentration of CAPE not only enhanced the oxygen-respiration of mitochondria but also increased the glycolysis in LNCaP C4-2B cells. Additionally, we observed that CAPE treatment reduced reactive oxygen species (ROS) in LNCaP C4-2B cells and activated AMPK pathway. Our results suggested that CAPE treatment alters the metabolism in PCa cells and thus contributes to the interference of the proliferation and survival of PCa cells.

誌謝 i
Abstract ii
中文摘要 iii
List of Figures vi
Abbreviation vii
CHAPTER 1 Introduction 1
1.1 Prostate and Prostate cancer 1
1.1.1 Prostate 1
1.1.2 Prostate cancer 1
1.1.3 Treatment of prostate cancer 2
1.2 Metabolism of cancer cells 3
1.2.1 Metabolism reprogramming 3
1.2.2 Warburg effect 4
1.3 Pentose phosphate pathway (PPP) 5
1.4 Oxidative stress and reactive oxygen species (ROS) 6
1.5 AMP-activated Protein Kinase (AMPK) Signaling 7
1.6 Caffeic acid phenethyl ester (CAPE) 8
CAPTER 2 The aim and flowchart of the study 9
2.1 The aim of the study 9
2.2 Experimental flowchart 9
CHAPTER 3 Material and Methods 10
3.1 Chemicals 10
3.2 Cell culture 10
3.3 Cell proliferation assay 10
3.4 Cell viability assay 11
3.5 Measurement of cellular bioenergetics 11
3.6 Quantitative real-time polymerase chain reaction (qRT-PCR) 12
3.7 Western blotting 13
3.8 Measurement of metabolites 14
3.9 Measurement of intracellular oxidative stress 15
3.10 Micro-Western array (MWA) 16
3.11 Statistical analysis 17
CHAPTER 4 Results 18
4.1 CAPE treatment significantly suppresses the cell proliferation and survival of LNCaP C4-2B human PCa cells 18
4.2 CAPE increases the bioenergetic function in LNCaP C4-2B cells 19
4.2.1 CAPE treatment enhances the oxygen consumption rate (OCR) 19
4.2.2 Extracellular acidification rate (ECAR) is increased by CAPE 19
4.3 Alteration of metabolic regulators by CAPE treatment 20
4.4 The cellular metabolites in LNCaP C4-2B cells treat by CAPE 21
4.5 CAPE reduces intracellular ROS in LNCaP C4-2B cells 22
4.6 AMPK pathway is activated by CAPE 22
4.7 The effects of long-term treatment with CAPE 20 µM 23
CHAPTER 5 Conclusions and Discussion 25
Figures and Figure Legends 27
References 44
Table. Antibody list 51
Supplementary Figures 56
Appendix 60

1. (2012). AMPK Maintains NADPH Levels during Energy Stress. Cancer Discovery 2.
2. Auciello, F.R., Ross, F.A., Ikematsu, N., and Hardie, D.G. (2014). Oxidative stress activates AMPK in cultured cells primarily by increasing cellular AMP and/or ADP. Febs Letters 588, 3361-3366.
3. Body, A., Pranavan, G., Tan, T.H., and Slobodian, P. (2018). Medical management of metastatic prostate cancer. Aust Prescr 41, 154-159.
4. Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A., and Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68, 394-424.
5. Chen, W.R., Yang, J.Q., Liu, F., Shen, X.Q., and Zhou, Y.J. (2020). Melatonin attenuates vascular calcification by activating autophagy via an AMPK/mTOR/ULK1 signaling pathway. Experimental Cell Research 389.
6. Chung, T.W., Moon, S.K., Chang, Y.C., Ko, J.H., Lee, Y.C., Cho, G., Kim, S.H., Kim, J.G., and Kim, C.H. (2004). Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism. Faseb Journal 18, 1670-1681.
7. Chuu, C.P., Lin, H.P., Ciaccio, M.F., Kokontis, J.M., Hause, R.J., Hiipakka, R.A., Liao, S.S., and Jones, R.B. (2012). Caffeic Acid Phenethyl Ester Suppresses the Proliferation of Human Prostate Cancer Cells through Inhibition of p70S6K and Akt Signaling Networks. Cancer Prevention Research 5, 788-797.
8. Ciaccio, M.F., Wagner, J.P., Chuu, C.P., Lauffenburger, D.A., and Jones, R.B. (2010). Systems analysis of EGF receptor signaling dynamics with microwestern arrays. Nat Methods 7, 148-155.
9. Cooper, E.H., Robinson, M.R.G., Whelan, P., and Ferro, M.A. (1992). TUMOR-MARKERS IN PROSTATE-CANCER. Cancer 70, 225-229.
10. Corbucci, G.G., Perrino, C., Donato, G., Ricchi, A., Lettieri, B., Troncone, G., Indolfi, C., Chiariello, M., and Avvedimento, E.V. (2004). Transient and reversible deoxyribonucleic acid damage in human left ventricle under controlled ischemia and reperfusion. Journal of the American College of Cardiology 43, 1992-1999.
11. Dinc, E., Ayaz, L., and Kurt, A.H. (2017). Protective Effect of Combined Caffeic Acid Phenethyl Ester and Bevacizumab Against Hydrogen Peroxide-Induced Oxidative Stress in Human RPE Cells. Curr Eye Res 42, 1659-1666.
12. Eid, H.M., Vallerand, D., Muhammad, A., Durst, T., Haddad, P.S., and Martineau, L.C. (2010). Structural constraints and the importance of lipophilicity for the mitochondrial uncoupling activity of naturally occurring caffeic acid esters with potential for the treatment of insulin resistance. Biochemical Pharmacology 79, 444-454.
13. Fouad, Y.A., and Aanei, C. (2017). Revisiting the hallmarks of cancer. American Journal of Cancer Research 7, 1016-1036.
14. Fraser, S.P., Hemsley, F., and Djamgoz, M.B.A. (2016). Caffeic acid phenethyl ester: Inhibition of metastatic cell behaviours via voltage-gated sodium channel in human breast cancer in vitro. International Journal of Biochemistry & Cell Biology 71, 111-118.
15. Garcia, D., and Shaw, R.J. (2017). AMPK: Mechanisms of Cellular Energy Sensing and Restoration of Metabolic Balance. Mol Cell 66, 789-800.
16. Hanahan, D., and Weinberg, R.A. (2011). Hallmarks of Cancer: The Next Generation. Cell 144, 646-674.
17. Harvey, C.J., Pilcher, J., Richenberg, J., Patel, U., and Frauscher, F. (2012). Applications of transrectal ultrasound in prostate cancer. Br J Radiol 85 Spec No 1, S3-17.
18. Herzig, S., and Shaw, R.J. (2018). AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol 19, 121-135.
19. Jang, M., Kim, S.S., and Lee, J. (2013). Cancer cell metabolism: implications for therapeutic targets. Exp Mol Med 45, e45.
20. Jeon, S.M., Chandel, N.S., and Hay, N. (2012). AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Nature 485, 661-665.
21. Jiang, P., Du, W., and Wu, M. (2014). Regulation of the pentose phosphate pathway in cancer. Protein Cell 5, 592-602.
22. Kathagen-Buhmann, A., Schulte, A., Weller, J., Holz, M., Herold-Mende, C., Glass, R., and Lamszus, K. (2016). Glycolysis and the pentose phosphate pathway are differentially associated with the dichotomous regulation of glioblastoma cell migration versus proliferation. Neuro-Oncology 18, 1219-1229.
23. Kitamura, K., Shirato, H., Shimizu, S., Shinohara, N., Harabayashi, T., Shimizu, T., Kodama, Y., Endo, H., Onimaru, R., Nishioka, S., et al. (2002). Registration accuracy and possible migration of internal fiducial gold marker implanted in prostate and liver treated with real-time tumor-tracking radiation therapy (RTRT). Radiotherapy and Oncology 62, 275-281.
24. Kuo, Y.Y., Huo, C., Lin, C.Y., Lin, H.P., Liu, J.S., Wang, W.C., Chang, C.R., and Chuu, C.P. (2019). Caffeic acid phenethyl ester suppresses androgen receptor signaling and stability via inhibition of phosphorylation on Ser81 and Ser213. Cell Commun Signal 17, 100.
25. Kurutas, E.B. (2016). The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutrition Journal 15.
26. Liberti, M.V., and Locasale, J.W. (2016). The Warburg Effect: How Does it Benefit Cancer Cells? Trends in Biochemical Sciences 41, 211-218.
27. Lin, H.P., Lin, C.Y., Huo, C., Hsiao, P.H., Su, L.C., Jiang, S.S., Chan, T.M., Chang, C.H., Chen, L.T., Kung, H.J., et al. (2015). Caffeic acid phenethyl ester induced cell cycle arrest and growth inhibition in androgen-independent prostate cancer cells via regulation of Skp2, p53, p21Cip1 and p27Kip1. Oncotarget 6, 6684-6707.
28. Liu, B.B., Deng, X.L., Jiang, Q.Q., Li, G.X., Zhang, J.L., Zhang, N., Xin, S.L., and Xu, K.S. (2020). Scoparone improves hepatic inflammation and autophagy in mice with nonalcoholic steatohepatitis by regulating the ROS/P38/Nrf2 axis and PI3K/AKT/mTOR pathway in macrophages. Biomedicine & Pharmacotherapy 125.
29. Liu, R., Li, W., Tao, B., Wang, X., Yang, Z., Zhang, Y., Wang, C., Liu, R., Gao, H., Liang, J., et al. (2019). Tyrosine phosphorylation activates 6-phosphogluconate dehydrogenase and promotes tumor growth and radiation resistance. Nat Commun 10, 991.
30. Lobo, V., Patil, A., Phatak, A., and Chandra, N. (2010). Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn Rev 4, 118-126.
31. Lu, J., Tan, M., and Cai, Q. (2015). The Warburg effect in tumor progression: mitochondrial oxidative metabolism as an anti-metastasis mechanism. Cancer Lett 356, 156-164.
32. Lubos, E., Loscalzo, J., and Handy, D.E. (2011). Glutathione peroxidase-1 in health and disease: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal 15, 1957-1997.
33. Marberger, M., Carroll, P.R., Zelefsky, M.J., Coleman, J.A., Hricak, H., Scardino, P.T., and Abenhaim, L.L. (2008). New Treatments for Localized Prostate Cancer. Urology 72, 36-43.
34. Mele, L., Paino, F., Papaccio, F., Regad, T., Boocock, D., Stiuso, P., Lombardi, A., Liccardo, D., Aquino, G., Barbieri, A., et al. (2018). A new inhibitor of glucose-6-phosphate dehydrogenase blocks pentose phosphate pathway and suppresses malignant proliferation and metastasis in vivo. Cell Death & Disease 9.
35. Michaluart, P., Masferrer, J.L., Carothers, A.M., Subbaramaiah, K., Zweifel, B.S., Koboldt, C., Mestre, J.R., Grunberger, D., Sacks, P.G., Tanabe, T., et al. (1999). Inhibitory effects of caffeic acid phenethyl ester on the activity and expression of cyclooxygenase-2 in human oral epithelial cells and in a rat model of inflammation. Cancer Research 59, 2347-2352.
36. Mullarky, E., and Cantley, L.C. (2015). Diverting Glycolysis to Combat Oxidative Stress. In Innovative Medicine: Basic Research and Development, K. Nakao, N. Minato, and S. Uemoto, eds. (Tokyo), pp. 3-23.
37. Murtaza, G., Karim, S., Akram, M.R., Khan, S.A., Azhar, S., Mumtaz, A., and Bin Asad, M.H. (2014). Caffeic acid phenethyl ester and therapeutic potentials. Biomed Res Int 2014, 145342.
38. Natarajan, K., Singh, S., Burke, T.R., Grunberger, D., and Aggarwal, B.B. (1996). Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B. Proceedings of the National Academy of Sciences of the United States of America 93, 9090-9095.
39. Nie, J.R., Chang, Y.N., Li, Y.J., Zhou, Y.J., Qin, J.W., Sun, Z., and Li, H.B. (2017). Caffeic Acid Phenethyl Ester (Propolis Extract) Ameliorates Insulin Resistance by Inhibiting JNK and NF-kappa B Inflammatory Pathways in Diabetic Mice and HepG2 Cell Models. Journal of Agricultural and Food Chemistry 65, 9041-9053.
40. Otto, A.M. (2016). Warburg effect(s)-a biographical sketch of Otto Warburg and his impacts on tumor metabolism. Cancer Metab 4, 5.
41. Pacifici, R.E., and Davies, K.J.A. (1991). PROTEIN, LIPID AND DNA-REPAIR SYSTEMS IN OXIDATIVE STRESS - THE FREE-RADICAL THEORY OF AGING REVISITED. Gerontology 37, 166-180.
42. Patra, K.C., and Hay, N. (2014). The pentose phosphate pathway and cancer. Trends Biochem Sci 39, 347-354.
43. Pavlova, N.N., and Thompson, C.B. (2016). The Emerging Hallmarks of Cancer Metabolism. Cell Metab 23, 27-47.
44. Phan, L.M., Yeung, S.C., and Lee, M.H. (2014). Cancer metabolic reprogramming: importance, main features, and potentials for precise targeted anti-cancer therapies. Cancer Biol Med 11, 1-19.
45. Phaniendra, A., Jestadi, D.B., and Periyasamy, L. (2015). Free radicals: properties, sources, targets, and their implication in various diseases. Indian J Clin Biochem 30, 11-26.
46. Raat, N.J.H., Shiva, S., and Gladwin, M.T. (2009). Effects of nitrite on modulating ROS generation following ischemia and reperfusion. Advanced Drug Delivery Reviews 61, 339-350.
47. Richardson, S.R., and O'Malley, G.F. (2020). Glucose 6 Phosphate Dehydrogenase (G6PD) Deficiency. In StatPearls (Treasure Island (FL)).
48. Richter, E.A., and Ruderman, N.B. (2009). AMPK and the biochemistry of exercise: implications for human health and disease. Biochem J 418, 261-275.
49. Riddick, D.S., Ding, X.X., Wolf, C.R., Porter, T.D., Pandey, A.V., Zhang, Q.Y., Gu, J., Finn, R.D., Ronseaux, S., McLaughlin, L.A., et al. (2013). NADPH-Cytochrome P450 Oxidoreductase: Roles in Physiology, Pharmacology, and Toxicology. Drug Metabolism and Disposition 41, 12-23.
50. Riganti, C., Gazzano, E., Polimeni, M., Aldieri, E., and Ghigo, D. (2012). The pentose phosphate pathway: an antioxidant defense and a crossroad in tumor cell fate. Free Radic Biol Med 53, 421-436.
51. Ruiz-Pesini, E., Lopez-Gallardo, E., Dahmani, Y., Herrero, M.D., Solano, A., Diez-Sanchez, C., Lopez-Perez, M., and Montoya, J. (2006). Diseases of the human mitochondrial oxidative phosphorylation system. Revista De Neurologia 43, 416-424.
52. Sadeghi-Nejad, H., Simmons, M., Dakwar, G., and Dogra, V. (2006). Controversies in transrectal ultrasonography and prostate biopsy. Ultrasound Q 22, 169-175.
53. Sanders, E., and Diehl, S. (2015). Analysis and interpretation of transcriptomic data obtained from extended Warburg effect genes in patients with clear cell renal cell carcinoma. Oncoscience 2, 151-186.
54. Shiratori, R., Furuichi, K., Yamaguchi, M., Miyazaki, N., Aoki, H., Chibana, H., Ito, K., and Aoki, S. (2019). Glycolytic suppression dramatically changes the intracellular metabolic profile of multiple cancer cell lines in a mitochondrial metabolism-dependent manner. Sci Rep 9, 18699.
55. Smith, M.R., Saad, F., Chowdhury, S., Oudard, S., Hadaschik, B.A., Graff, J.N., Olmos, D., Mainwaring, P.N., Lee, J.Y., Uemura, H., et al. (2018). Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med 378, 1408-1418.
56. Snezhkina, A.V., Kudryavtseva, A.V., Kardymon, O.L., Savvateeva, M.V., Melnikova, N.V., Krasnov, G.S., and Dmitriev, A.A. (2019). ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells. Oxid Med Cell Longev 2019, 6175804.
57. Stanton, R.C. (2012a). Glucose-6-phosphate dehydrogenase, NADPH, and cell survival. IUBMB Life 64, 362-369.
58. Stanton, R.C. (2012b). Glucose-6-phosphate dehydrogenase, NADPH, and cell survival. Iubmb Life 64, 362-369.
59. Stoyanova, T., Cooper, A.R., Drake, J.M., Liu, X., Armstrong, A.J., Pienta, K.J., Zhang, H., Kohn, D.B., Huang, J., Witte, O.N., et al. (2013). Prostate cancer originating in basal cells progresses to adenocarcinoma propagated by luminal-like cells. Proc Natl Acad Sci U S A 110, 20111-20116.
60. Tolba, M.F., Azab, S.S., Khalifa, A.E., Abdel-Rahman, S.Z., and Abdel-Naim, A.B. (2013). Caffeic acid phenethyl ester, a promising component of propolis with a plethora of biological activities: a review on its anti-inflammatory, neuroprotective, hepatoprotective, and cardioprotective effects. IUBMB Life 65, 699-709.
61. Tolba, M.F., Omar, H.A., Azab, S.S., Khalifa, A.E., Abdel-Naim, A.B., and Abdel-Rahman, S.Z. (2016). Caffeic Acid Phenethyl Ester: A Review of Its Antioxidant Activity, Protective Effects against Ischemia-reperfusion Injury and Drug Adverse Reactions. Crit Rev Food Sci Nutr 56, 2183-2190.
62. Tseng, J.C., Lin, C.Y., Su, L.C., Fu, H.H., Yang, S.D., and Chuu, C.P. (2016). CAPE suppresses migration and invasion of prostate cancer cells via activation of non-canonical Wnt signaling. Oncotarget 7, 38010-38024.
63. Vander Heiden, M.G., Cantley, L.C., and Thompson, C.B. (2009). Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324, 1029-1033.
64. Viollet, B., and Andreelli, F. (2011). AMP-activated protein kinase and metabolic control. Handb Exp Pharmacol, 303-330.
65. Viollet, B., Horman, S., Leclerc, J., Lantier, L., Foretz, M., Billaud, M., Giri, S., and Andreelli, F. (2010). AMPK inhibition in health and disease. Crit Rev Biochem Mol Biol 45, 276-295.
66. Wadosky, K.M., and Koochekpour, S. (2016). Therapeutic Rationales, Progresses, Failures, and Future Directions for Advanced Prostate Cancer. Int J Biol Sci 12, 409-426.
67. Wallis, C.J.D., Klaassen, Z., Bhindi, B., Goldberg, H., Chandrasekar, T., Farrell, A.M., Boorjian, S.A., Kulkarni, G.S., Karnes, R.J., and Satkunasivam, R. (2018). Comparison of Abiraterone Acetate and Docetaxel with Androgen Deprivation Therapy in High-risk and Metastatic Hormone-naive Prostate Cancer: A Systematic Review and Network Meta-analysis. European Urology 73, 834-844.
68. Wang, T., Chen, L., Wu, W., Long, Y., and Wang, R. (2008a). Potential cytoprotection: antioxidant defence by caffeic acid phenethyl ester against free radical-induced damage of lipids, DNA, and proteins. Can J Physiol Pharmacol 86, 279-287.
69. Wang, T., Chen, L.X., Wu, W.M., Long, Y., and Wang, R. (2008b). Potential cytoprotection: antioxidant defence by caffeic acid phenethyl ester against free radical-induced damage of lipids, DNA, and proteins. Canadian Journal of Physiology and Pharmacology 86, 279-287.
70. Wu, W.M., Lu, L., Long, Y., Wang, T., Liu, L., Chen, Q., and Wang, R. (2007). Free radical scavenging and antioxidative activities of caffeic acid phenethyl ester (CAPE) and its related compounds in solution and membranes: A structure-activity insight. Food Chemistry 105, 107-115.
71. Wu, Y., Dong, Y., Song, P., and Zou, M.H. (2012). Activation of the AMP-activated protein kinase (AMPK) by nitrated lipids in endothelial cells. PLoS One 7, e31056.
72. Xiang, D.B., Wang, D., He, Y.J., Xie, J., Zhong, Z.Y., Li, Z.P., and Xie, J. (2006). Caffeic acid phenethyl ester induces growth arrest and apoptosis of colon cancer cells via the beta-catenin/T-cell factor signaling. Anti-Cancer Drugs 17, 753-762.
73. Yang, H.C., Cheng, M.L., Hua, Y.S., Wu, Y.H., Lin, H.R., Liu, H.Y., Ho, H.Y., and Chiu, D.T.Y. (2015). Glucose 6-phosphate dehydrogenase knockdown enhances IL-8 expression in HepG2 cells via oxidative stress and NF-kappa B signaling pathway. Journal of Inflammation-London 12.
74. Zhang, D., Zhao, S., Li, X., Kirk, J.S., and Tang, D.G. (2018). Prostate Luminal Progenitor Cells in Development and Cancer. Trends Cancer 4, 769-783.
75. Zheng, J. (2012). Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation (Review). Oncol Lett 4, 1151-1157.