title: 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.
authors.affiliation: Laboratory of Marine Natural Product, College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Soma
authors.initials: S
authors.lastname: Kundu
authors.affiliation: Laboratory of Molecular Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Tae Hyung
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Laboratory of Marine Natural Product, College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Food Science and Biotechnology, Dongguk University-Seoul, Seoul 100-715, Republic of Korea.
authors.forename: Han-Seung
authors.initials: HS
authors.lastname: Shin
authors.affiliation: Laboratory of Marine Natural Product, College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Jaewon
authors.initials: J
authors.lastname: Lee
authors.affiliation: Laboratory of Marine Natural Product, College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Jee H
authors.initials: JH
authors.lastname: Jung
authors.affiliation: Laboratory of Molecular Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D008870:Microtubules / Q000187:drug effects / Q000235:genetics; D009284:Naphthols / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D008869:Microtubule-Associated Proteins; D009284:Naphthols; C010375:viriditoxin