Cannabidiol-induced apoptosis is mediated by activation of Noxa in human colorectal cancer cells

Cancer Lett. 2019 Apr 10;447:12-23. doi: 10.1016/j.canlet.2019.01.011. Epub 2019 Jan 18.

Abstract

Cannabidiol (CBD), one of the compounds present in the marijuana plant, has anti-tumor properties, but its mechanism is not well known. This study aimed to evaluate the apoptotic action of CBD in colorectal cancer (CRC) cells, and focused on its effects on the novel pro-apoptotic Noxa-reactive oxygen species (ROS) signaling pathway. CBD experiments were performed using the CRC cell lines HCT116 and DLD-1. CBD induced apoptosis by regulating many pro- and anti-apoptotic proteins, of which Noxa showed significantly higher expression. To understand the relationship between Noxa and CBD-induced apoptosis, Noxa levels were downregulated using siRNA, and the expression of apoptosis markers decreased. After ROS production was blocked, the level of Noxa also decreased, suggesting that ROS is involved in the regulation of Noxa, which along with ROS is a well-known pro-apoptotic signaling agents. As a result, CBD induced apoptosis in a Noxa-and-ROS-dependent manner. Taken together, the results obtained in this study re-demonstrated the effects of CBD treatment in vivo, thus confirming its role as a novel, reliable anticancer drug.

Keywords: Apoptotic cell death; Bcl-2 protein family; Colon cancer; Marijuana extract; ROS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Cannabidiol / pharmacology*
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism*
  • HCT116 Cells
  • Humans
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • PMAIP1 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Cannabidiol