Methanolic Extract from Sea Cucumber, Holothuria scabra, Induces Apoptosis and Suppresses Metastasis of PC3 Prostate Cancer Cells Modulated by MAPK Signaling Pathway

J Microbiol Biotechnol. 2021 Jun 28;31(6):775-783. doi: 10.4014/jmb.2103.03034.


Sea cucumber, Holothuria scabra, is a well-known traditional Asian medicine that has been used for suppressing inflammation, promoting wound healing, and improving immunity. Moreover, previous studies demonstrated that the extract from H. scabra contains many bioactive compounds with potent inhibitory effect on tumor cell survival and progression. However, the effect of the methanolic extract from the body wall of H. scabra (BWMT) on human prostate cancer cells has not yet been investigated. In this study, we aimed to investigate the effects and underlying mechanism of BWMT on prostate cancer cell viability and metastasis. BWMT was obtained by maceration with methanol. The effect of BWMT on cell viability was assessed by MTT and colony formation assays. The intracellular ROS accumulation was evaluated using a DCFH-DA fluorescence probe. Hoechst 33342 staining and Annexin V-FITC/PI staining were used to examine the apoptotic-inducing effect of the extract. A transwell migration assay was performed to determine the anti-metastasis effect. BWMT significantly reduced cell viability and triggered cellular apoptosis by accumulating intracellular ROS resulting in the upregulation of JNK and p38 signaling pathways. In addition, BWMT also inhibited the invasion of PC3 cells by downregulating MMP-2/-9 expression via the ERK pathway. Consequently, our study provides BWMT from H. scabra as a putative therapeutic agent that could be applicable against prostate cancer progression.

Keywords: Holothuria scabra; MAPK; ROS; apoptosis; metastasis; prostate cancer.

MeSH terms

  • Animals
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Cycle Checkpoints / drug effects
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Holothuria / chemistry*
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Methanol / chemistry
  • PC-3 Cells
  • Prostatic Neoplasms / pathology*
  • Reactive Oxygen Species / metabolism


  • Antineoplastic Agents
  • Reactive Oxygen Species
  • Methanol