Department of Biotechnology, Science Campus, Alagappa University, Karaikudi, 630 003, Tamil Nadu, India.
National Facility for Drug Development (NFDD) for Academia, Pharmaceutical and Allied Industries, Bharathidasan Institute of Technology, Anna University, Tiruchirappalli, 620024, Tamil Nadu, India.
Sci Rep. 2017 Jun 13;7(1):3418. doi: 10.1038/s41598-017-03511-4.
Lung cancer is the leading cause of cancer related deaths both in developed and developing countries. Since majority of the existing therapeutic methods harms both normal and malignant cells, a viable alternative is to switch into safe and beneficial traditional medicinal plants. Hence the present study was framed to identify selective anti-lung cancer agents from the medicinal plant Grewia tiliaefolia (GT). Cell viability experiments showed that benzene extract of GT (BGT) leaf effectively inhibited the growth of A549 cells, while being non-toxic to normal human lung L132 and PBMC cells. Ames and comet assays demonstrated that BGT is of non-mutagenic and non-genotoxic nature in untransformed cells. The hematological and histopathological profiles of the in vivo acute and sub-acute toxicity studies demonstrated that BGT is safe and tolerable. Importantly, western blot analysis and Annexin V-FITC staining confirmed that BGT promotes mitochondrial dependent apoptotic cell death in A549 cells by arresting cell cycle at G2/M phase. Bio-assay guided fractionation revealed the presence of phytosteols (β-sitosterol and daucosterol) which significantly inhibited the growth of A549 cells both alone and in combination. This study warrants that these phytosterols in alone or in combination can be considered as safe and potential drug candidates for lung cancer treatment.
肺癌是发达国家和发展中国家癌症相关死亡的主要原因。由于大多数现有的治疗方法会损害正常和恶性细胞，因此需要寻找一种可行的替代方法，即使用安全且有益的传统药用植物。因此，本研究旨在从药用植物番石榴（GT）中鉴定出具有选择性的抗肺癌药物。细胞活力实验表明，GT 的苯提取物（BGT）叶有效地抑制了 A549 细胞的生长，而对正常的人肺 L132 和 PBMC 细胞没有毒性。Ames 和彗星试验表明，BGT 在未转化细胞中是非致突变和非遗传毒性的。体内急性和亚急性毒性研究的血液学和组织病理学分析表明，BGT 通过将细胞周期阻滞在 G2/M 期，在 A549 细胞中促进线粒体依赖性凋亡细胞死亡，是安全且可耐受的。重要的是，Western blot 分析和 Annexin V-FITC 染色证实，BGT 通过阻滞细胞周期在 G2/M 期，促进 A549 细胞发生线粒体依赖性凋亡细胞死亡。生物活性测定指导的分离揭示了植物甾醇（β-谷甾醇和豆甾醇）的存在，它们单独和联合使用时都能显著抑制 A549 细胞的生长。这项研究表明，这些植物甾醇单独或联合使用时可以被认为是治疗肺癌的安全且有潜力的药物候选物。
