Agarwal Rajesh, Agarwal Charu, Ichikawa Haruyo, Singh Rana P, Aggarwal Bharat B
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Anticancer Res. 2006 Nov-Dec;26(6B):4457-98.
Silymarin consists of a family of flavonoids (silybin, isosilybin, silychristin, silydianin and taxifoline) commonly found in the dried fruit of the milk thistle plant Silybum marianum. Although silymarin's role as an antioxidant and hepatoprotective agent is well known, its role as an anticancer agent has begun to emerge. Extensive research within the last decade has shown that silymarin can suppress the proliferation of a variety of tumor cells (e.g., prostate, breast, ovary, colon, lung, bladder); this is accomplished through cell cycle arrest at the G1/S-phase, induction of cyclin-dependent kinase inhibitors (such as p15, p21 and p27), down-regulation of anti-apoptotic gene products (e.g., Bcl-2 and Bcl-xL), inhibition of cell-survival kinases (AKT, PKC and MAPK) and inhibition of inflammatory transcription factors (e.g., NF-kappaB). Silymarin can also down-regulate gene products involved in the proliferation of tumor cells (cyclin D1, EGFR, COX-2, TGF-beta, IGF-IR), invasion (MMP-9), angiogenesis (VEGF) and metastasis (adhesion molecules). The antiinflammatory effects of silymarin are mediated through suppression of NF-kappaB-regulated gene products, including COX-2, LOX, inducible iNOS, TNF and IL-1. Numerous studies have indicated that silymarin is a chemopreventive agent in vivo against a variety of carcinogens/tumor promoters, including UV light, 7,12-dimethylbenz(a)anthracene (DMBA), phorbol 12-myristate 13-acetate (PMA) and others. Silymarin has also been shown to sensitize tumors to chemotherapeutic agents through down-regulation of the MDR protein and other mechanisms. It binds to both estrogen and androgen receptors, and down-regulates PSA. In addition to its chemopreventive effects, silymarin exhibits antitumor activity against human tumors (e.g., prostate and ovary) in rodents. Various clinical trials have indicated that silymarin is bioavailable and pharmacologically safe. Studies are now in progress to demonstrate the clinical efficacy of silymarin against various cancers.
水飞蓟素是一类黄酮类化合物（水飞蓟宾、异水飞蓟宾、水飞蓟亭、水飞蓟宁和 taxifoline）的统称，常见于水飞蓟属植物水飞蓟的干燥果实中。尽管水飞蓟素作为抗氧化剂和肝脏保护剂的作用广为人知，但其作为抗癌剂的作用也已开始显现。过去十年的广泛研究表明，水飞蓟素可抑制多种肿瘤细胞（如前列腺癌、乳腺癌、卵巢癌、结肠癌、肺癌、膀胱癌）的增殖；这是通过使细胞周期停滞在 G1/S 期、诱导细胞周期蛋白依赖性激酶抑制剂（如 p15、p21 和 p27）、下调抗凋亡基因产物（如 Bcl-2 和 Bcl-xL）、抑制细胞存活激酶（AKT、PKC 和 MAPK）以及抑制炎症转录因子（如 NF-κB）来实现的。水飞蓟素还可下调参与肿瘤细胞增殖（细胞周期蛋白 D1、表皮生长因子受体、环氧合酶-2、转化生长因子-β、胰岛素样生长因子-1 受体）、侵袭（基质金属蛋白酶-9）、血管生成（血管内皮生长因子）和转移（黏附分子）的基因产物。水飞蓟素的抗炎作用是通过抑制 NF-κB 调节的基因产物介导的，这些产物包括环氧合酶-2、脂氧合酶、诱导型一氧化氮合酶、肿瘤坏死因子和白细胞介素-1。众多研究表明，水飞蓟素在体内是一种化学预防剂，可对抗多种致癌物/肿瘤启动剂，包括紫外线、7,12-二甲基苯并(a)蒽（DMBA）、佛波酯 12-肉豆蔻酸 13-乙酸酯（PMA）等。水飞蓟素还被证明可通过下调多药耐药蛋白和其他机制使肿瘤对化疗药物敏感。它与雌激素和雄激素受体结合，并下调前列腺特异性抗原。除了其化学预防作用外，水飞蓟素在啮齿动物中对人类肿瘤（如前列腺癌和卵巢癌）具有抗肿瘤活性。各种临床试验表明，水飞蓟素具有生物利用度且在药理学上是安全的。目前正在进行研究以证明水飞蓟素对各种癌症的临床疗效。
