Chapter 8 - Role of Gambogic Acid in Chemosensitization of Cancer

Abstract

Mother Nature has blessed us with a variety of natural compounds rich in anti-inflammatory and anti-tumor properties. In the past three decades, plant-derived natural compounds, popularly referred to as nutraceuticals, have received a lot of attention because they are economic, bioavailable, safe, and lethal to cancers. One of noteworthy nutraceuticals is gambogic acid (GA). GA that is derived from gamboge resins secreted by a plant known as Garcinia hanburyi. Extensive preclinical studies have strongly suggested that GA possesses anti-cancer properties against a variety of malignancies including solid and hematologic cancers. GA exerts its effects on cancer cells through several different mechanisms. Interestingly, normal human cells were found to be resistant to GA, suggesting that this nutraceutical has tremendous therapeutic values. Chemoresistance has been recognized as one of the largest hurdles facing anti-cancer regimens. Therefore, researchers have continued to search for potent chemosensitizers. This chapter focuses on the chemosensitizing properties of GA, mechanisms through which GA exerts anti-proliferative and apoptotic effects in cancer. GA sensitizes acute myeloid leukemia (AML), gastric cancer, lung cancer, ovarian cancer, prostate cancer, pancreatic cancer, renal carcinoma, and multiple myeloma (MM). GA acts synergistically with many chemotherapeutic agents including adriamycin, cisplatin, doxorubicin, 5-fluorouracil (5-FU), gefitinib, and proteasome inhibitors. Overall, in vitro and studies using animal models demonstrate that GA can be used to sensitize tumors to chemotherapy. Nonetheless, a clinical trial is needed in order to fully delineate the utility of this nutraceutical in human cancers.