Chalones – From Aqueous Extracts To Oligopeptides

Abstract

The term "chalone" was coined about 40 years ago to describe endogenous growthinhibiting factors with a tissue-specific and reversible effect. A large number of "chalones" were reported in the 1970's and early 80's. The term was, however, used rather indiscriminately and attempts at purification of the active component(s) were without success. As a result, most laboratories lost interest. Then, in the early 1980's, two different research teams demonstrated that the active growth-inhibiting constituents were N-substituted oligopeptides. In the following years, similar oligopeptides were characterized in extracts of liver, the large bowel, melanocytes, lymphocytes, and neuroblastoma, in addition to the two first ones from monomyelopoietic cells and epidermis, respectively. All peptides have a bell-shaped dose response pattern and optimal effect at very low concentrations. Several of them inhibit growth even in tumors derived from the respective organs. Preliminary studies have revealed that two of the oligopeptides alter the expression of growth-and differentiation-related genes. Quite recently, some papers are again using the term "chalone" and a short review therefore seems appropriate.

Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly

“…YAP transcriptionally activates cell cycle proteins such as Ki-67 and c-Myc and also inhibitors of apoptosis, and its phosphorylation by way of activation of the 'Hippo' pathway blocks its ability to shuttle to the nucleus [17]. The Hippo pathway is considered to be a 'size checkpoint' operating at the level of the organ's total mass, perhaps reminiscent of the 'chalone' hypothesis that was fashionable in the 1970s, which held that the size of each organ was controlled by a tissue-specific chalone, produced by differentiated cells, that negatively regulated the progenitor compartment [18,19]. .…”

A Cell Biology Inspired Model for Managing Packet Broadcasts in Mobile Ad-hoc Networks

“…Bullough [19] coined the term "chalone" and hypothesized it as the inhibitors of cell growth through negative feedback to control the size of a tissue. A number of studies provide experimental 4 evidence in support of this hypothesis [20], [21], [22], [23].The growth in terms of the level of functionality is sensed for example, in the liver by the flux of bile acids. Bile acids are synthesized in the liver and secreted into the small intestine to facilitate digestion.…”

SMT and TOFT: Why and How They are Opposite and Incompatible Paradigms

“…Indeed, experimental data show that proliferation is physiologically under the control of negative feedback regulators. The hypothesis of tissue control of proliferation (chalones) goes back to the 1950s, and it gained some acceptability in the 1990s (Elgjo and Reichelt 2004)with the discovery of myostatin and its role as a feedback controller of muscle growth (Lee and McPherron 1999). Since then, several other chalones have been identified in various tissues, many of which are claimed to be members of the TGFb family (Gamer et al 2003).…”