Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia.
Molecules. 2012 Sep 10;17(9):10816-30. doi: 10.3390/molecules170910816.
Jatropha meal produced from the kernel of Jatropha curcas Linn. grown in Malaysia contains phorbol esters (PEs). The potential benefits of PEs present in the meal as anticancer agent are still not well understood. Hence, this study was conducted to evaluate the cytotoxic effects and mode of actions of PEs isolated from Jatropha meal against breast (MCF-7) and cervical (HeLa) cancer cell lines. Isolated PEs inhibited cells proliferation in a dose-dependent manner of both MCF-7 and HeLa cell lines with the IC₅₀ of 128.6 ± 2.51 and 133.0 ± 1.96 µg PMA equivalents/mL respectively, while the values for the phorbol 12-myristate 13-acetate (PMA) as positive control were 114.7 ± 1.73 and 119.6 ± 3.73 µg/mL, respectively. Microscopic examination showed significant morphological changes that resemble apoptosis in both cell lines when treated with PEs and PMA at IC₅₀ concentration after 24 h. Flow cytometry analysis and DNA fragmentation results confirmed the apoptosis induction of PEs and PMA in both cell lines. The PEs isolated from Jatropha meal activated the PKC-δ and down-regulated the proto-oncogenes (c-Myc, c-Fos and c-Jun). These changes probably led to the activation of Caspase-3 protein and apoptosis cell death occurred in MCF-7 and HeLa cell lines upon 24 h treatment with PEs and PMA. Phorbol esters of Jatropha meal were found to be promising as an alternative to replace the chemotherapeutic drugs for cancer therapy.
从马来西亚种植的麻疯树内核中提取的麻疯树饼含有佛波酯（PEs）。PEs 作为抗癌剂的潜在益处尚未得到很好的理解。因此，本研究旨在评估从麻疯树饼中分离出的 PEs 对乳腺癌（MCF-7）和宫颈癌（HeLa）细胞系的细胞毒性作用和作用机制。分离出的 PEs 以剂量依赖的方式抑制 MCF-7 和 HeLa 细胞系的细胞增殖，IC₅₀ 值分别为 128.6 ± 2.51 和 133.0 ± 1.96 µg PMA 当量/mL，而阳性对照物佛波醇 12-肉豆蔻酸 13-乙酸酯（PMA）的 IC₅₀ 值分别为 114.7 ± 1.73 和 119.6 ± 3.73 µg/mL。显微镜检查显示，在用 PEs 和 PMA 处理后，在 24 小时达到 IC₅₀ 浓度时，两种细胞系均出现类似凋亡的形态学变化。流式细胞术分析和 DNA 片段化结果证实了 PEs 和 PMA 诱导两种细胞系发生凋亡。从麻疯树饼中分离出的 PEs 激活了蛋白激酶 C-δ并下调了原癌基因（c-Myc、c-Fos 和 c-Jun）。这些变化可能导致 Caspase-3 蛋白的激活，并且在用 PEs 和 PMA 处理 24 小时后，MCF-7 和 HeLa 细胞系发生凋亡性细胞死亡。麻疯树饼中的佛波酯有望成为替代化疗药物治疗癌症的一种选择。
