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In this article, the general pharmacological toxicity of gambogic acid (GA), a new anticancer agent, on the dog cardiovascular and respiratory system and the mouse central nervous system (CNS) were observed. The developmental toxicity and analgesic activities of GA were also investigated in rats and mice. Results showed that GA did not cause any toxic symptoms on blood pressure (i.e., mean arterial pressure), heart rate (HR), and respiratory frequency. However, a high dose of GA showed slight side effects on the mouse CNS. Further, evidence of maternal and developmental toxicity was observed in a dose-dependent manner. The maternal body-weight gain, as well as the birth weights and live birth index, were decreased significantly in the treatment groups. The inhibitory effects of GA on fetal skeletal development were also found. No obvious effects of GA on external alterations and visceral alterations were shown. In the analgesic experiments, GA showed significant analgesic activity in the acetic-acid-induced writhing study in a dose-dependent manner. This mechanism might be related to its anti-inflammation properties.

It is reported that gambogic acid (GA), the main active compound of gamboge which is a dry resin extracted from Garcinia hanburyi tree, has potent antitumor activity both in vivo and in vitro. Activation of mitochondrial apoptotic pathway in cancer cells is one effective therapy for cancer treatment. In the present study, we focus on the effect of GA on induction of reactive oxygen species (ROS) accumulation and triggering the mitochondrial signaling pathway in human hepatoma SMMC-7721 cells. The results indicated that GA induced ROS accumulation and collapse of mitochondrial membrane potential in SMMC-7721 cells in a concentration-dependent manner and subsequently induced that release of Cytochrome c and apoptosis-inducing factor from mitochondria to cytosol, which inhibited ATP generation and induced apoptosis in the cells. Moreover, GA elevated the phosphorylation of c-Jun-N-terminal protein kinase (JNK) and p38, which was the downstream effect of ROS accumulation. Furthermore, N-acetylcysteine, a ROS production inhibitor, partly reversed the activation of JNK and p38 and the induction of apoptosis in GA-treated cells. Collectively, our study demonstrated that accumulation of ROS played an important role in GA-induced mitochondrial signaling pathway, which provided further theoretical support for the application of GA as a promising anticancer agent.

Acute and chronic toxicity of gambogic acid, a promising novel anticancer agent, was determined using albino mice and Beagle dogs as model animals. Histopathological examination and viscera parameter investigation were also carried out after autopsy. The LD50 of gambogic acid was found to be 45 approximately 96 mg/kg and the 95% confidence limit was determined to be 43.18 approximately 48.45 mg/kg. The results from the chronic toxicity studies demonstrated that the toxicity targets in the experimental animals were liver and kidney. The innocuous dose was established to be 4 mg/kg after administration to dogs for a total of 13 weeks at a frequency of one injection every other day. This dose (4 mg/kg) was approximately 9.6 (body weight) or 5.1 (body surface area) times the dosage (25 mg/60 kg, every other day) recommended for human trials. Our results provide the theoretical foundation for clinical applications of this promising natural anticancer agent and will likely bring about considerable economic and social benefits.

It is an innovative way to diagnose with cancer with monoclonal antibody (MAb)in vivo.1–3 After proving MAb 2F7 (IgG2a) had a higher affinity and better specificity to human small cell lung cancer cells inin vitro,4,5 and gave a very clear cut γ- camera pictures for the xenografts of human small cell lung cancer (SCLC) born by nude mice,6 the possibility of clinical radioimmunoimaging was studied with the MAb 2F7 and its fragment F (ab′) 2.