Gambogic acid A

Gambogic Acid and Piperine Synergistically Induce Apoptosis in Human Cholangiocarcinoma Cell via Caspase and Mitochondria-Mediated Pathway.[Pubmed:35600948]

Evid Based Complement Alternat Med. 2022 May 12;2022:6288742.

Most cholangiocarcinoma (CCA) patients undergo chemotherapy as a therapeutic approach due to the disease's frequently late diagnosis. However, because CCA is resistant to currently available treatments, the prognosis for this cancer is still quite poor. Combination therapy has emerged as a novel and promising strategy in cancer treatment, as monotherapy frequently results in tumor recurrence and drug resistance. Gambogic acid has been shown to have a synergism with other compounds in combating certain cancer cells. Moreover, piperine has been shown to improve the efficacy of numerous chemotherapy drugs and other anticancer natural substances. However, no research has been done on the combination of these two compounds in the treatment of bile duct cancer. In this study, the cytotoxic activity was determined by using the MTT assay, and then, the combined effect was assessed by using the combination index (CI). We found that the combination of Gambogic acid And piperine inhibited cell viability more effectively than either treatment alone, and it also demonstrated a synergistically cytotoxic effect against CCA cells. Interestingly, the findings allowed the use of lower concentrations of gambogic acid in cancer treatment when combined with piperine, which could reduce its adverse effect on normal cholangiocytes. Furthermore, the combination of the two compounds increased CCA cell death by inducing apoptosis via both the extrinsic and intrinsic or mitochondria-mediated pathways, as determined by caspase-3, -8, and -9 activity and the reduction of mitochondrial transmembrane potential (DeltaPsim). It is possible that the use of these two natural compounds together could be a promising strategy for the treatment of bile duct cancer.

Research Progress in the Field of Gambogic Acid and Its Derivatives as Antineoplastic Drugs.[Pubmed:35566290]

Molecules. 2022 May 4;27(9). pii: molecules27092937.

Gambogic acid (GA) is a natural product with a wide range of pharmacological properties. It plays an important role in inhibiting tumor growth. A large number of GA derivatives have been designed and prepared to improve its shortcomings, such as poor water solubility, low bioavailability, poor stability, and adverse drug effects. So far, GA has been utilized to develop a variety of active derivatives with improved water solubility and bioavailability through structural modification. This article summarized the progress in pharmaceutical chemistry of GA derivatives to provide a reference and basis for further study on structural modifications of GA and expansion of its clinical applications.