Beta-endorphin cell therapy for cancer prevention.
β-Endorphin (BEP)-producing neuron in the hypothalamus plays a key role in bringing the stress axis to a state of homeostasis and maintaining body immune defense system. Long-term delivery of BEP to obtain beneficial effect on chemoprevention is challenging, as the peptides rapidly develop tolerance. Using rats as animal models, we show here that transplantation of BEP neurons into the hypothalamus suppressed carcinogens- and hormone-induced cancers in various tissues and prevented growth and metastasis of established tumors via activation of innate immune functions. In addition, we show that intracerebroventricular administration of nanosphere-attached dibutyryl cyclic adenosine monophosphate (dbcAMP) increased the number of BEP neurons in the hypothalamus, reduced the stress response, enhanced the innate immune function, and prevented tumor cell growth, progression, and metastasis. BEP neuronal supplementation did not produce any deleterious effects on general health but was beneficial in suppressing age-induced alterations in physical activity, metabolic, and immune functions. We conclude that the neuroimmune system has significant control over cancer growth and progression, and that activation of the neuroimmune system via BEP neuronal supplementation/induction may have therapeutic value for cancer prevention and improvement of general health.
Rutgers Endocrine Program, The State University of New Jersey, New Brunswick, New Jersey. Endocrinology and Animal Biosciences Graduate Program, Rutgers, The State University of New Jersey, New Brunswick, New Jersey.
Changqing
C
Zhang
Rutgers Endocrine Program, The State University of New Jersey, New Brunswick, New Jersey. Department of Animal Sciences, The State University of New Jersey, New Brunswick, New Jersey.
Sengottuvelan
S
Murugan
Rutgers Endocrine Program, The State University of New Jersey, New Brunswick, New Jersey. Department of Animal Sciences, The State University of New Jersey, New Brunswick, New Jersey.
Nadka
N
Boyadjieva
Rutgers Endocrine Program, The State University of New Jersey, New Brunswick, New Jersey. Endocrinology and Animal Biosciences Graduate Program, Rutgers, The State University of New Jersey, New Brunswick, New Jersey.
Shaima
S
Jabbar
Rutgers Endocrine Program, The State University of New Jersey, New Brunswick, New Jersey. Department of Animal Sciences, The State University of New Jersey, New Brunswick, New Jersey.
Pallavi
P
Shrivastava
Rutgers Endocrine Program, The State University of New Jersey, New Brunswick, New Jersey. Endocrinology and Animal Biosciences Graduate Program, Rutgers, The State University of New Jersey, New Brunswick, New Jersey. Department of Animal Sciences, The State University of New Jersey, New Brunswick, New Jersey. sarkar@aesop.rutgers.edu.
Dipak K
DK
Sarkar
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D003994:Bucladesine / Q000737:chemistry; D002273:Carcinogens / Q000737:chemistry; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005260:Female; D005951:Glucose Tolerance Test; D007031:Hypothalamus / Q000378:metabolism; D007107:Immune System; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000378:metabolism; D008297:Male; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000517:prevention & control*; D009474:Neurons / Q000637:transplantation*; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude; D017207:Rats, Sprague-Dawley; D001615:beta-Endorphin / Q000378:metabolism*
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D001615:beta-Endorphin; D003994:Bucladesine