Summary: | 博士 === 高雄醫學大學 === 天然藥物研究所博士班 === 103 === Physalis angulate of the family Solanaceae possesses antibacterial and anti-inflammatory effects, and exhibits cytotoxicity in human tumor cell lines. P. angulate extract contains numerous components, such as physalins which are cytotoxic compounds. Extant research has shown that inflammatory responses are highly correlated with cancer and thrombus formation. Thus, employing anti-inflammatory mechanisms to control or treat cancer and thrombus has become an emerging strategy. Among the various types of skin cancer, melanoma shows a higher death rate and rapid metastasis. Nevertheless, few chemotherapeutic agents are available for treating melanoma. The present study shows that the toxic mechanism of physalin B, which is used for fighting melanoma cells (A375, A2058; IC 50 < 4.6 μg/ml), takes effect through apoptosis. Western blot analysis indicated that NOXA expression was induced after 2 hour of stimulation with 3 μg/ml physalin B. Subsequently, Bax and caspase-3 were also induced in the A375 cell line, which lacks tumor necrosis factor (TNF)-related apoptosis-inducing ligand (Apo2L/TRAIL). These results indicate that physalin B induces the apoptosis of A375 through the mitochondrial channel. The experiment results also confirm that physalin B does not affect fibroblast and myoblast cells. Therefore, physalin B is potentially a suitable chemotherapeutic agent for treating malignant melanoma.
Research confirms that inflammation is a significant risk factor for thrombosis formation; however, few studies have addressed the influence of physalin B on platelet function. The present study examined the influence of physalin B on inhibiting platelet activation and thrombosis formation. The results indicate that 10 μM physalin B can inhibit human platelet activation through an arachidonic acid pathway and block the activation of P2Y12 receptors. Physalin B also exhibits an antiplatelet function without affecting the function of plasma coagulation factors. In addition, 80 μM physalin B can reduce the adhesion between TNF-??-induced THP-1 and endothelial cells. The results further confirm that the antithrombotic activity of physalin B originates from its anti-platelet and anti-inflammatory effects.
|