Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Evid Based Complement Alternat Med. 2014;2014:248103. doi: 10.1155/2014/248103. Epub 2014 Apr 7.
Persea declinata (Bl.) Kosterm is a member of the Lauraceae family, widely distributed in Southeast Asia. It is from the same genus with avocado (Persea americana Mill), which is widely consumed as food and for medicinal purposes. In the present study, we examined the anticancer properties of Persea declinata (Bl.) Kosterm bark methanolic crude extract (PDM). PDM exhibited a potent antiproliferative effect in MCF-7 human breast cancer cells, with an IC50 value of 16.68 µg/mL after 48 h of treatment. We observed that PDM caused cell cycle arrest and subsequent apoptosis in MCF-7 cells, as exhibited by increased population at G0/G1 phase, higher lactate dehydrogenase (LDH) release, and DNA fragmentation. Mechanistic studies showed that PDM caused significant elevation in ROS production, leading to perturbation of mitochondrial membrane potential, cell permeability, and activation of caspases-3/7. On the other hand, real-time PCR and Western blot analysis showed that PDM treatment increased the expression of the proapoptotic molecule, Bax, but decreased the expression of prosurvival proteins, Bcl-2 and Bcl-xL, in a dose-dependent manner. These findings imply that PDM could inhibit proliferation in MCF-7 cells via cell cycle arrest and apoptosis induction, indicating its potential as a therapeutic agent worthy of further development.
番木瓜(Persea declinata (Bl.) Kosterm)是樟科的一员,广泛分布于东南亚。它与鳄梨(Persea americana Mill)同属一科,被广泛食用或药用。在本研究中,我们研究了番木瓜(Bl.)Kosterm 树皮甲醇粗提物(PDM)的抗癌特性。PDM 在 MCF-7 人乳腺癌细胞中表现出很强的增殖抑制作用,处理 48 小时后,IC50 值为 16.68μg/mL。我们观察到 PDM 导致 MCF-7 细胞周期停滞和随后的细胞凋亡,表现为 G0/G1 期细胞群增加、乳酸脱氢酶(LDH)释放增加和 DNA 片段化。机制研究表明,PDM 导致 ROS 产生显著增加,导致线粒体膜电位、细胞通透性紊乱,并激活 caspase-3/7。另一方面,实时 PCR 和 Western blot 分析表明,PDM 处理以剂量依赖性方式增加促凋亡分子 Bax 的表达,但降低了抗凋亡蛋白 Bcl-2 和 Bcl-xL 的表达。这些发现表明,PDM 可通过细胞周期停滞和凋亡诱导抑制 MCF-7 细胞增殖,表明其具有作为治疗剂的潜力,值得进一步开发。