Immunomodulation-mediated anticancer activity of a novel compound from Brugmansia suaveolens leaves

Bioorg Med Chem. 2020 Jun 15;28(12):115552. doi: 10.1016/j.bmc.2020.115552. Epub 2020 May 11.

Abstract

Immunomodulation activity-guided fractionation of ethanol extract of Brugmansia suaveolens leaves was carried out to isolate a novel compound SUPH036-022A (1) by co-culturing the test fraction/compound activated PBMC with MCF7 and A549 cancer cell lines. Assessment of immune markers in PBMC, and analysis of apoptosis markers and cell cycle was carried out for cancer cells. The structure of the isolated compound was elucidated by spectral analysis. Compound 1 enhanced the secretion of immune markers, IL-2 and IFN-γ, from PBMC. Further, compound 1 treated PBMC increased cell death in MCF7 and A549 cell lines and induced ROS production and mitochondrial membrane perturbation, leading to apoptosis. Flow cytometry analysis revealed; compound 1 stimulated PBMC to cause a five-fold increase in cell cycle perturbations in the sub-G1 stage of cancer cells as compared to the negative control. The compound, in the absence of PBMC, only had a weak cytotoxic activity against these cell lines. Thus, compound 1 is a novel lead for immunomodulation-mediated anticancer activity.

Keywords: Apoptosis; Bioactivity-guided fractionation; Brugmansia suaveolens; Cancer; Immunomodulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects
  • Brugmansia / chemistry*
  • Brugmansia / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Plant Extracts / chemistry
  • Plant Leaves / chemistry
  • Plant Leaves / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Interleukin-2
  • Plant Extracts
  • Reactive Oxygen Species
  • Interferon-gamma