Laminarin-Derived from Brown Algae Suppresses the Growth of Ovarian Cancer Cells via Mitochondrial Dysfunction and ER Stress

Mar Drugs. 2020 Mar 9;18(3):152. doi: 10.3390/md18030152.

Abstract

Ovarian cancer (OC) is difficult to diagnose at an early stage and leads to the high mortality rate reported in the United States. Standard treatment for OC includes maximal cytoreductive surgery followed by platinum-based chemotherapy. However, relapse due to chemoresistance is common in advanced OC patients. Therefore, it is necessary to develop new anticancer drugs to suppress OC progression. Recently, the anticancer effects of laminarin, a beta-1,3-glucan derived from brown algae, have been reported in hepatocellular carcinoma, colon cancer, leukemia, and melanoma. However, its effects in OC are not reported. We confirmed that laminarin decreases cell growth and cell cycle progression of OC cells through the regulation of intracellular signaling. Moreover, laminarin induced cell death through DNA fragmentation, reactive oxygen species generation, induction of apoptotic signals and endoplasmic reticulum (ER) stress, regulation of calcium levels, and alteration of the ER-mitochondria axis. Laminarin was not cytotoxic in a zebrafish model, while in a zebrafish xenograft model, it inhibited OC cell growth. These results suggest that laminarin may be successfully used as a novel OC suppressor.

Keywords: ER stress; cell death; laminarin; mitochondria; ovarian cancer.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor / drug effects*
  • Endoplasmic Reticulum Stress / drug effects
  • Female
  • Glucans / pharmacology
  • Glucans / therapeutic use*
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Ovarian Neoplasms / drug therapy*
  • Phaeophyceae*
  • Phytotherapy

Substances

  • Antineoplastic Agents
  • Glucans
  • laminaran