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Viriditoxin regulates apoptosis and autophagy via mitotic catastrophe and microtubule formation in human prostate cancer cells.

Abstract
Microtubule targeting chemicals are considered excellent antitumor drugs through their binding to tubulin, which affects the instability of microtubules resulting in arrest of cancer cells. The present study was designed to investigate the antitumor effects of viriditoxin (VDT) against human prostate cancer cells. VDT, isolated from Paecilomyces variotii fungus, which was derived from the jellyfish Nemopilema nomurai, offers a new approach for controlling resistant bacterial infections by blocking bacterial cell division proteins. VDT produced dose-dependent cytotoxicity against human prostate cancer cells. Treatment with VDT promoted both apoptosis and autophagy in LNCaP cells. Annexin V/FITC staining indicated that apoptosis occurred in VDT-treated LNCaP cells. DAPI staining revealed morphological changes in the cell nuclei indicative of mitotic catastrophe in LNCaP cells. VDT caused cell growth inhibition via G2/M phase arrest. Moreover, VDT also increased autophagic cell death in LNCaP cells by induction of several autophagy-related proteins such as LC3 II, Atg5, Atg7 and beclin-1 protein, which are essential for autophagy induction. These results were also confirmed by acridine orange staining. This study indicates that VDT could potentially be effective against prostate cancer by promoting multiple modes of growth arrest and cell death coupled with apoptosis and autophagy.
AuthorsSoma Kundu, Tae Hyung Kim, Jung Hyun Yoon, Han-Seung Shin, Jaewon Lee, Jee H Jung, Hyung Sik Kim
JournalInternational journal of oncology (Int J Oncol) Vol. 45 Issue 6 Pg. 2331-40 (Dec 2014) ISSN: 1791-2423 [Electronic] Greece
PMID25231051 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Microtubule-Associated Proteins
  • Naphthols
  • viriditoxin
Topics
  • Apoptosis (drug effects)
  • Autophagy (drug effects)
  • Cell Line, Tumor
  • Humans
  • Male
  • Microtubule-Associated Proteins (biosynthesis)
  • Microtubules (drug effects, genetics)
  • Naphthols (administration & dosage)
  • Prostatic Neoplasms (drug therapy, genetics, pathology)

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