a-Solanine被發現存在於許多天然茄科植物中，包括馬鈴薯 (Solanum tuberosum)、番茄 (Solanum lycopersicum) 及茄子 (Solanum melongena) 等。目前有許多研究指出a-solanine具有抑制腫瘤細胞增生及促進細胞凋亡等特性。先前本實驗室發現，a-solanine藉由抑制MMP-2 (matrix metalloproteinase-2) 及MMP-9之表現進而抑制人類黑色素瘤細胞爬行與侵入。本研究測試a-solanine對人類前列腺癌細胞 (PC-3) 侵入能力之抑制效果。實驗結果顯示，隨a-solanine劑量的增加，可有效抑制人類前列腺癌細胞PC-3之增殖。當以無毒性之a-solanine劑量 (12 uM) 處理PC-3細胞時，對於細胞侵入之能力有顯著抑制之效果。此外，a-solanine可抑制MMP-9與EMMPRIN，亦可增加RECK之基因表現。再者，我們的研究發現，a-solanine可抑制ERK與JNK蛋白的磷酸化。另外，a-solanine亦可以顯著的降低核內轉錄因子NF-kB之蛋白量，顯示a-solanine可抑制轉錄因子NF-kB的活性。綜合以上結果，a-solanine可能藉由抑制磷酸化的ERK與JNK之訊息傳遞路徑及NF-kB之活性，進而影響MMP-9, EMMPRIN與RECK之基因表現，進而達到抑制人類前列腺癌細胞PC-3侵入之效果。 a-Solanine occurs naturally in many species of the genus Solanum, including the potato (Solanum tuberosum), tomato (Solanum lycopersicum) and eggplant (Solanum melongena). a-Solanine was found to possess anti-carcinogenic property, such as inhibiting proliferation and inducing apoptosis of tumor cells. Recently, we demonstrated that a-solanine suppressed migration and invasion of human melanoma cells through reducing matrix metalloproteinase-2 and -9 (MMP-2 and -9) expression. In the present study, we examined the inhibitory effect of a-solanine on metastasis of prostate cancer cell PC-3 in vitro. Data indicated the a-solanine can inhibit proliferation of human prostate cancer PC-3 cell in a dose-dependent manner. When treated with non-toxic doses of a-solanine, cell invasion ability was inhibited significantly. The mRNA level of MMP-9, extracellular inducer of matrix metalloproteinase (EMMPRIN) were also suppressed while reversion-inducing-cysteine-rich protein with kazal motifs (RECK) were increased by a-solanine. Our biochemical assays indicated that a-solanine potently suppressed the phosphorylation of extracellular signal-regulated kinases (ERK) and c-Jun N-terminal kinase (JNK). In addition, a-solanine significantly decreased the nuclear level of nuclear factor kappa B (NF-kB), suggesting that a-solanine inhibited NF-kB activity. Taken together, the results suggested that a-solanine inhibited invasion of PC-3 cells by reducing expressions of MMP-9, EMMPRIN and RECK. It also inhibited ERK and JNK signaling pathways as well as NF-kB activity.
