Butea monosperma (Lam.) Taub. Bark fractions protect against free radicals and induce apoptosis in MCF-7 breast cancer cells via cell-cycle arrest and ROS-mediated pathway

Drug Chem Toxicol. 2020 Jul;43(4):398-408. doi: 10.1080/01480545.2018.1497051. Epub 2018 Oct 8.

Abstract

Butea monosperma (Lam.) Taub. is an ethnomedicinal tree of remedial value in the treatment of diabetes, bone fractures, and liver and neurological disorders. However, the information available on DNA-protective and anti-proliferative potential of bark of this tree is scarce. In the present study, the extract/fractions obtained from bark of B. monosperma were evaluated for antioxidant, DNA-protective, and anti-proliferative activities, along with their phytochemical profiling for identifying major constituents present in them. Different extract/fractions, namely, Bmth (methanol), Bhex (hexane), Bchl (chloroform), and Beac (ethyl acetate), were prepared and evaluated for antioxidant activity using in vitro assays. Extract/fractions were also evaluated for anti-proliferative and apoptotic activity in human breast carcinoma cell line MCF-7, using in vitro assays, namely, MTT, clonogenic, and neutral comet assay, along with confocal microscopy and flow cytometry. Among all extract/fractions, a pronounced antioxidant activity was exhibited by Bchl and Beac fractions, in DPPH· (EC50 213.2 and 161.5 µg/mL, respectively), ABTS+· (EC50 139.3 and 44.1 µg/mL, respectively), and reducing power assay (EC50 86.7 and 84.5 µg/mL, respectively). Both fractions protected plasmid DNA against hydroxyl radical induced damage in plasmid nicking assay. Bchl and Beac were also observed to inhibit the growth of MCF-7 cells (GI50 203.7 and 246.5 µg/mL, respectively). Both fractions induced apoptosis in MCF-7 cells, by arresting the cell cycle in G1 and sub-G1 phase, respectively, enhancing ROS levels, decreasing mitochondrial membrane potential, and inducing double-strand DNA breaks. HPLC analysis revealed high kaempferol content in Bchl, and catechin, epicatechin, and gallic acid in Beac.

Keywords: Butea monosperma; MCF-7; ROS; antioxidant; apoptosis; cell cycle.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antioxidants / pharmacology
  • Apoptosis / drug effects*
  • Breast Neoplasms / pathology*
  • Butea / chemistry*
  • Cell Cycle Checkpoints / drug effects
  • Female
  • Humans
  • MCF-7 Cells
  • Medicine, Ayurvedic*
  • Plant Bark / chemistry*
  • Plant Extracts / pharmacology*
  • Reactive Oxygen Species / antagonists & inhibitors*

Substances

  • Antineoplastic Agents, Phytogenic
  • Antioxidants
  • Plant Extracts
  • Reactive Oxygen Species