Phorbol esters: structure, biological activity, and toxicity in animals

Phorbol esters are the tetracyclic diterpenoids generally known for their tumor promoting activity. The phorbol esters mimic the action of diacyl glycerol (DAG), activator of protein kinase C, which regulates different signal transduction pathways and other cellular metabolic activities. They occur naturally in many plants of the family Euphorbiacaeae and Thymelaeaceae. The biological activities of the phorbol esters are highly structure specific. The phorbol esters, even at very low concentrations, show toxicological manifestations in animals fed diets containing them. This toxicity limits the use of many nutritive plants and agricultural by-products containing phorbol esters to be used as animal feed. Therefore, various chemical and physical treatments have been evaluated to extract or inactivate phorbol esters so that seed meals rich in proteins could be used as feed resources. However, not much progress has been reported so far. The detoxifying ability has also been reported in some molluscs and in liver homogenate of mice. Besides, possessing antinutritional and toxic effects, few derivatives of the phorbol esters are also known for their antimicrobial and antitumor activities. The molluscicidal and insecticidal properties of phorbol esters indicate its potential to be used as an effective biopesticide and insecticide.