ABSTRACT
Cancerous cells are detrimental to the human body and can be incredibly resilient against treatments because of the complexities of molecular carcinogenic pathways. In particular, cancer cells are able to sustain increased growth under metabolic stress due to phenomena like the Warburg effect. Krüppel-like factor 4 (KLF4), a context-dependent transcription factor that can act as both a tumor suppressor and an oncogene, is involved in many molecular pathways that respond to low glucose and increased reactive oxygen species (ROS), raising the question of its role in metabolic stress as a result of increased proliferation of tumor cells. In this study, metabolic assays were performed, showing enhanced efficiency of energy production in cells expressing KLF4. Western blotting showed that KLF4 increases the expression of essential glycolytic proteins. Furthermore, we used immunostaining to show that KLF4 increases the localization of glucose transporter 1 (GLUT1) to the cellular membrane. 2',7'-Dichlorodihydrofluorescein diacetate (H2DCF-DA) was used to analyze the production of ROS, and we found that KLF4 reduces stress-induced ROS within cells. Finally, we demonstrated increased autophagic death in KLF4-expressing cells in response to glucose starvation. Collectively, these results relate KLF4 to non-Warburg metabolic behaviors that support its role as a tumor suppressor and could make KLF4 a target for new cancer treatments.
Subject(s)
Homeostasis , Kruppel-Like Transcription Factors/metabolism , Stress, Physiological , Animals , Autophagy , Cell Membrane/metabolism , Energy Metabolism/genetics , Gene Expression Regulation , Glucose/deficiency , Glucose Transporter Type 1/metabolism , Glycolysis/genetics , Kruppel-Like Factor 4 , Kruppel-Like Transcription Factors/genetics , Mice, Inbred C57BL , Models, Biological , Reactive Oxygen Species/metabolism , Stress, Physiological/geneticsABSTRACT
Tibetan medicine is known as the knowledge of healing in the Four Tantras, the main medical text studied by Tibetan doctors. In the 8th century, King Trisong Deutsen (718-785 CE) invited eminent physicians from India, China, Persia, East Turkestan, Mongolia, and Nepal for the First International Medical Symposium in Samye, Tibet and ordered his personal physician Elder Yuthog Yonten Gonpo (708-833 CE), who lived 125 years, and participated in this conference to summarize. By combining all the information available and presented during this symposium, he compiled the Four Tantras. He established the Tanadug medical school at Menlung in Kongpo, Southern Tibet in 763 CE, and worked for the propagation of Tibetan medicine. He is considered an emanation of Medicine Buddha, who is a symbol of mental and physical well being. In his left hand, the Medicine Buddha clasps a begging bowl with long-life nectar, signifying immortality, and in his right, the Chebulic myrobalan (Haritaki), a symbol of good health. Chebulic myrobalan, Belleric myrobalan, and Emblic myrobalan are together called the "3 Fruits" and are common ingredients in Tibetan medicines. Prof. Omura, Y of NY Medical College evaluated these "3 Fruits" and found that one of them available as a "Haritaki," had the highest normal cell telomere increasing effect by optimal dose, with improvement of circulation all over the body, which in turn inhibits cancer activity. He considered Tibetan medicine to be the most advanced medicine in the world before the 19th Century with its well-organized systematic method as described by colorful Tibetan medical paintings by Sangye Gyamtso (1653-1705 CE). During a typical diagnosis, the physician examines the patients' tongue, radial arteries for pulse beats by the index, middle, and ring fingers of both hands and the urine for features like color, vapor, and bubbles, etc.
Subject(s)
Medicine, Tibetan Traditional/methods , Phytotherapy/methods , Plants, Medicinal/chemistry , History, 15th Century , History, 16th Century , History, 17th Century , History, 18th Century , History, 19th Century , History, 20th Century , History, Ancient , History, Medieval , Humans , Medicine, Tibetan Traditional/history , Phytotherapy/historyABSTRACT
The theory and practice of traditional Tibetan medicine (TTM) is based on an understanding of a tri-level psycho-physical system; this bi-directional connection between the psycho-somatic realms is mediated by a distinct, yet inseparable energetic system--the subtle body. TTM practitioners approach both diagnosis and treatment from an understanding of this subtle energetic system. In the Tibetan yogic tradition, control of this system via advanced yogic and meditative technologies is the path to realize extraordinary levels of health, happiness, and longevity. As a result, understanding this intricately linked philosophical, medical, and yogic system is critical for engaging in dialogue about longevity-enhancement within this tradition.
Subject(s)
Adaptation, Psychological/physiology , Medicine, Tibetan Traditional/methods , Humans , Longevity , Meditation , YogaABSTRACT
This paper is intended to serve as a traditional Tibetan medical response to advancements in basic longevity research, with particular attention to current models of caloric restriction. This is a complicated task, as Tibetan medicine traditionally approaches dietary modification from a radically different perspective, and relies upon a complex model of health and balance in the treatment and prevention of disease. This paper offers a brief overview of the traditional Tibetan medicine (TTM) model and suggests potential areas for collaborative research on dietary modification.
