Division of Biological Science and Research Center for Women's Diseases, Sookmyung Women's University, Seoul 140-742, South Korea.
Food Chem Toxicol. 2012 Mar;50(3-4):648-52. doi: 10.1016/j.fct.2011.11.007. Epub 2011 Nov 15.
Angelica genus (umbelliferae) has traditionally been used as the medicine and health food considered alleviating several used in the treatment of cancer as well as non-cancerous diseases. Angelica purpuraefolia Chung is an endemic species and a folk medicine in Korea. We have previously reported that two natural khellactone isolated from the rhizomes of A. purpuraefolia has significant antiplasmodial activity against Plasmodium falciparum. In the present study, we scientifically evaluated the effect of (+)-4'-decanoyl-cis-khellactone and (+)-3'-decanoyl-cis-khellactone from A. purpuraefolia on cell proliferation and apoptotic cell death. The anti-proliferative and apoptotic effects of (+)-4'-decanoyl-cis-khellactone and (+)-3'-decanoyl-cis-khellactone (10-50 μg/ml) were subjected to in vitro evaluation using four breast (MDA-MB-231, MCF-7, HS578T, and T47D), three cervical (HeLa, SiHa, and C33A) cancer cell lines, and NIH 3T3 normal cells using FACS and western analyses. Our in vitro experiments showed that (+)-4'-decanoyl-cis-khellactone and (+)-3'-decanoyl-cis-khellactone suppress the growth and proliferation of cancer cells at a relatively low concentration (<10 μg/ml) and induce apoptosis at a high concentration (>50 μg/ml). FACS analysis showed that the cell cycle arrest in the S/G2 phase was induced by the treatment with 10 μg/ml of (+)-4'-decanoyl-cis-khellactone and (+)-3'-decanoyl-cis-khellactone in MDA-MB-231 cells. Western blot analysis also showed that concentration higher than 50 μg/ml of (+)-4'-decanoyl-cis-khellactone induced a time-dependent increase in the percentage of apoptotic cells. However, our results showed that (+)-4'-decanoyl-cis-khellactone uses both extrinsic and intrinsic pathways but (+)-3'-decanoyl-cis-khellactone uses only an intrinsic pathway for the apoptosis. More importantly, (+)-4'-decanoyl-cis-khellactone and (+)-3'-decanoyl-cis-khellactone inhibited the in vitro proliferation of six other human breast and cervical cancer cell lines. Our data strongly suggest that (+)-4'-decanoyl-cis-khellactone and (+)-3'-decanoyl-cis-khellactone act as an anti-cancer supplement particularly against breast and cervical cancers by inducing cell cycle arrest in the S/G2 phase and caspase-dependent apoptosis at relatively low and high concentrations, respectively.
当归还被传统用作治疗癌症和非癌症疾病的药物和保健品。紫花前胡是韩国的特有种和民间药物。我们之前报道过，从紫花前胡根茎中分离出的两种天然贝壳杉烯具有抗疟原虫活性，对恶性疟原虫有显著的抑制作用。在本研究中，我们从科学角度评估了(+)-4'-癸酰基-顺式贝壳杉烯和(+)-3'-癸酰基-顺式贝壳杉烯对细胞增殖和凋亡细胞死亡的影响。采用流式细胞术和western blot 分析，研究了(+)-4'-癸酰基-顺式贝壳杉烯和(+)-3'-癸酰基-顺式贝壳杉烯(10-50μg/ml)对体外四种乳腺癌(mda-mb-231、mcg-7、hs578t 和 t47d)、三种宫颈癌(hela、sih 和 c33a)和nih 3t3 正常细胞系的增殖和凋亡作用。我们的体外实验表明，(+)-4'-癸酰基-顺式贝壳杉烯和(+)-3'-癸酰基-顺式贝壳杉烯在相对较低的浓度(<10μg/ml)下抑制癌细胞的生长和增殖，并在较高的浓度(>50μg/ml)下诱导细胞凋亡。流式细胞术分析表明，10μg/ml 的(+)-4'-癸酰基-顺式贝壳杉烯和(+)-3'-癸酰基-顺式贝壳杉烯处理可诱导 mda-mb-231 细胞周期停滞在 s/g2 期。western blot 分析也表明，浓度高于 50μg/ml 的(+)-4'-癸酰基-顺式贝壳杉烯诱导凋亡细胞的百分比呈时间依赖性增加。然而，我们的结果表明，(+)-4'-癸酰基-顺式贝壳杉烯使用外源性和内源性途径，但(+)-3'-癸酰基-顺式贝壳杉烯仅使用内源性途径诱导细胞凋亡。更重要的是，(+)-4'-癸酰基-顺式贝壳杉烯和(+)-3'-癸酰基-顺式贝壳杉烯抑制了六种其他人类乳腺癌和宫颈癌细胞系的体外增殖。我们的数据强烈表明，(+)-4'-癸酰基-顺式贝壳杉烯和(+)-3'-癸酰基-顺式贝壳杉烯通过诱导 s/g2 期细胞周期停滞和 caspase 依赖性凋亡，分别在较低和较高浓度下发挥抗癌补充作用，特别是针对乳腺癌和宫颈癌。
