Division of Endocrinology, CSIR-Central Drug Research Institute-CDRI, U.P., Lucknow 226001, India.
J Ethnopharmacol. 2012 Jun 26;142(1):72-9. doi: 10.1016/j.jep.2012.04.015.
Wrightia tomentosa Roem. & Schult. (Apocynaceae) is known in the traditional medicine for anti-cancer activity along with other broad indications like snake and scorpion bites, renal complications, menstrual disorders etc. However, the anti-cancer activity of this plant or its constituents has never been studied systematically in any cancer types so far.
To evaluate the anti-cancer activities of the ethanolic extract of W. tomentosa and identified constituent active molecule(s) against breast cancer.
Powdered leaves of W. tomentosa were extracted with ethanol. The ethanolic extract, subsequent hexane fractions and fraction F-4 of W. tomentosa were tested for its anti-proliferative and pro-apoptotic effects in breast cancer cells MCF-7 and MDA-MB-231.
The ethanolic extract, subsequent hexane fractions and fraction F-4 of W. tomentosa inhibited the proliferation of human breast cancer cell lines, MCF-7 and MDA-MB-231. The fraction F-4 obtained from hexane fraction inhibited proliferation of MCF-7 and MDA-MB-231 cells in concentration and time dependent manner with IC₅₀ of 50 μg/ml and 30 μg/ml for 24 h, 28 μg/ml and 22 μg/ml for 48 h and 25 μg/ml and 20 μg/ml for 72 h respectively. The fraction F-4 induced G1 cell cycle arrest, reactive oxygen species (ROS) generation, loss of mitochondrial membrane potential and subsequent apoptosis. Apoptosis is indicated in terms of increased Bax/Bcl-2 ratio, enhanced Annexin-V positivity, caspase 8 activation and DNA fragmentation. The active molecule isolated from fraction F-4, oleanolic acid and urosolic acid inhibited cell proliferation of MCF-7 and MDA-MB-231 cells at IC₅₀ value of 7.5 μM and 7.0 μM respectively, whereas there is devoid of significant cell inhibiting activity in non-cancer originated cells, HEK-293. In both MCF-7 and MDA-MB-231, oleanolic acid and urosolic acid induced cell cycle arrest and apoptosis as indicated by significant increase in Annexin-V positive apoptotic cell counts.
Our results suggest that W. tomentosa extracts has significant anti-cancer activity against breast cancer cells due to induction of apoptosis pathway. Olenolic and urosolic acid are important constituent molecules in the extract responsible for anti-cancer activity of W. tomentosa.
夹竹桃科 Wrightia tomentosa Roem. & Schult. 因其具有抗癌活性以及抗蛇蝎咬伤、肾脏并发症、月经失调等广泛的适应症，在传统医学中广为人知。然而，迄今为止，尚未有针对任何癌症类型对该植物或其成分的抗癌活性进行系统研究。
评估 Wrightia tomentosa 的乙醇提取物及其鉴定的活性成分分子对乳腺癌的抗癌活性。
用乙醇提取 Wrightia tomentosa 的粉末状叶子。测试 Wrightia tomentosa 的乙醇提取物、后续的己烷级分和级分 F-4 对乳腺癌细胞 MCF-7 和 MDA-MB-231 的抗增殖和促凋亡作用。
Wrightia tomentosa 的乙醇提取物、后续的己烷级分和级分 F-4 抑制了人乳腺癌细胞系 MCF-7 和 MDA-MB-231 的增殖。从己烷级分中获得的级分 F-4 以浓度和时间依赖的方式抑制 MCF-7 和 MDA-MB-231 细胞的增殖，其 24 小时 IC₅₀ 为 50 μg/ml 和 30 μg/ml，48 小时 IC₅₀ 为 28 μg/ml 和 22 μg/ml，72 小时 IC₅₀ 为 25 μg/ml 和 20 μg/ml。该级分 F-4 诱导 G1 细胞周期停滞、活性氧 (ROS) 生成、线粒体膜电位丧失和随后的细胞凋亡。凋亡表现为 Bax/Bcl-2 比值增加、 Annexin-V 阳性增加、caspase 8 激活和 DNA 片段化。从级分 F-4 中分离出的活性分子，熊果酸和齐墩果酸，在 IC₅₀ 值为 7.5 μM 和 7.0 μM 时抑制 MCF-7 和 MDA-MB-231 细胞的增殖，而在非癌细胞起源的细胞 HEK-293 中则没有显著的细胞抑制活性。在 MCF-7 和 MDA-MB-231 中，熊果酸和齐墩果酸通过显著增加 Annexin-V 阳性凋亡细胞数量诱导细胞周期停滞和凋亡。
我们的结果表明，Wrightia tomentosa 提取物由于诱导凋亡途径而对乳腺癌细胞具有显著的抗癌活性。齐墩果酸和熊果酸是提取物中负责 Wrightia tomentosa 抗癌活性的重要成分分子。
