Anti-tumor Effect and Mechanism of Betulinic Acid： A Review / 中国实验方剂学杂志

ABSTRACT

Betulinic acid （BA） is a lupane pentacyclic triterpene extracted from a variety of Chinese herbs such as Betulae Platyphyllae Cortex， Astragali Radix， Paeoniae Radix Alba， Jujubae Fructus， Sanguisorbae Radix， Eucommiae Cortex， Glycrrhizae Radix et Rhizoma， Aucklandiae Radix， and Ziziphi Spinosae Semen. It has attracted wide attention from doctors because of its low toxicity， high efficacy， and multiple functions. BA has been found to possess a significant anti-tumor biological activity， and it is expected to become a potential drug for the treatment of malignant tumors. So far， a number of studies have shown that BA is able to promote apoptosis， inhibit proliferation， metastasis and invasion， and induce cell cycle arrest via multiple mechanisms， thus resisting various malignant tumors such as ovarian cancer， breast cancer， gastric cancer， lung cancer， colorectal cancer， and prostate cancer. It exerts the anti-tomor effect by regulating the expression of cancer suppressor genes p53 and p21， triggering the generatoipn of reactive oxygen species （ROS）， down-regulating the expression of nuclear transcription factor-κB （NF-κB）， adjusting the B lymphocytoma-2 （Bcl-2） family to cause tumor cell apoptosis， and regulating transcription factor Sp1/3/4 to induce apoptosis. Its anti-proliferative activity is mainly achieved via the regulation of cyclin B， cyclin D and cyclin dependent kinases CDK and CDC. Its efficacy in inhibiting metastasis and invasion is mainly realized by regulating matrix metalloproteinase （MMP） and matrix metalloproteinase inhibitor （TIMP）， up-regulating E-cadherin， down-regulating N-cadherin and blocking the epithelial-mesenchymal transformation （EMT）. In addition， BA also induces cell cycle arrest， affects tumor metabolic reprogramming， and activates autophagy to inhibit tumor. Although there are a large number of studies on BA against tumors and its efficacy has been proved strong， the systematic review on its anti-tumor effect is still lacking. Therefore， this study reviewed the anti-tumor effect and mechanism of BA， in order to provide reference for its subsenquent research.