Indian Council of Medical Research-National Institute of Pathology, Safdarjung Hospital Campus, New Delhi, India.
PATH.Org, New Delhi, India.
Med Oncol. 2024 May 8;41(6):143. doi: 10.1007/s12032-024-02397-3.
Picrorhiza kurroa, an "Indian gentian," a known Himalayan medicinal herb with rich source of phytochemicals like picrosides I, II, and other glycosides, has been traditionally used for the treatment of liver and respiratory ailments. Picrosides anti-proliferative, anti-oxidant, anti-inflammatory and other pharmacological properties were evaluated in treating triple-negative breast cancer (TNBC). Picroside I and II were procured from Sigma-Aldrich and were analyzed for anti-cancer activity in triple-negative breast cancer (MDA-MB-231) cells. Cell viability was analyzed using MTT and trypan blue assays. Apoptosis was analyzed through DNA fragmentation and Annexin V/PI flow cytometric analysis. Wound healing and cell survival assays were employed to determine the inhibition of invasion capacity and anti-proliferative activity of picrosides in MDA-MB-231 cells. Measurement of intracellular ROS was studied through mitochondrial membrane potential assessment using DiOC6 staining for anti-oxidant activity of picrosides in MDA-MB-231 cells. Both Picroside I and II have shown decreased cell viability of MDA-MB-231 cells with increasing concentrations. IC values of 95.3 µM and 130.8 µM have been obtained for Picroside I and II in MDA-MB-231 cells. Early apoptotic phase have shown an increase of 20% (p < 0.05) with increasing concentrations (0, 50, 75, and 100 µM) of Picroside I and 15% (p < 0.05) increase with Picroside II. Decrease in mitochondrial membrane potential of 2-2.5-fold (p < 0.05) was observed which indicated decreased reactive oxygen species (ROS) generation with increasing concentrations of Picroside I and II. An increasing percentage of 70-80% (p < 0.05) cell population was arrested in G0/G1 phase of cell cycle after Picroside I and II treatment in cancer cells. Our results suggest that Picroside I and II possess significant anti-proliferative and anti-cancer activity which is mediated by inhibition of cell growth, decreased mitochondrial membrane potential, DNA damage, apoptosis, and cell cycle arrest. Therefore, Picroside I and II can be developed as a potential anti-cancer drug of future and further mechanistic studies are underway to identify the mechanism of anti-cancer potential.
波棱瓜子，一种“印度龙胆”，是一种已知的喜马拉雅药用植物，含有丰富的生物活性化合物，如番木鳖苷 I、II 和其他糖苷。传统上用于治疗肝脏和呼吸道疾病。番木鳖苷的抗增殖、抗氧化、抗炎和其他药理学特性已在治疗三阴性乳腺癌 (TNBC) 中进行了评估。从西格玛-奥德里奇 (Sigma-Aldrich) 获得了番木鳖苷 I 和 II，并在三阴性乳腺癌 (MDA-MB-231) 细胞中分析了其抗癌活性。使用 MTT 和台盼蓝测定法分析细胞活力。通过 DNA 片段化和 Annexin V/PI 流式细胞术分析分析细胞凋亡。通过伤口愈合和细胞存活测定来确定番木鳖苷对 MDA-MB-231 细胞侵袭能力的抑制和抗增殖活性。通过 DiOC6 染色评估线粒体膜电位来研究细胞内 ROS 的测量，以研究番木鳖苷在 MDA-MB-231 细胞中的抗氧化活性。番木鳖苷 I 和 II 均显示出 MDA-MB-231 细胞活力随着浓度的增加而降低。在 MDA-MB-231 细胞中，番木鳖苷 I 和 II 的 IC 值分别为 95.3µM 和 130.8µM。随着番木鳖苷 I 浓度（0、50、75 和 100µM）的增加，早期凋亡阶段增加了 20%（p<0.05），而番木鳖苷 II 增加了 15%（p<0.05）。观察到线粒体膜电位降低 2-2.5 倍（p<0.05），表明随着番木鳖苷 I 和 II 浓度的增加，活性氧 (ROS) 的产生减少。在癌细胞中用番木鳖苷 I 和 II 处理后，细胞周期中 G0/G1 期的细胞群增加了 70-80%（p<0.05）。我们的结果表明，番木鳖苷 I 和 II 具有显著的抗增殖和抗癌活性，这是通过抑制细胞生长、降低线粒体膜电位、DNA 损伤、细胞凋亡和细胞周期停滞来介导的。因此，番木鳖苷 I 和 II 可以开发为未来的潜在抗癌药物，并且正在进行进一步的机制研究以确定其抗癌潜力的机制。
