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

Kundu,Soma; Kim,Tae Hyung; Yoon,Jung Hyun; Shin,Han-Seung; Lee,Jaewon; Jung,Jee H.; Kim,Hyung Sik

doi:10.3892/ijo.2014.2659

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

Authors:
- Soma Kundu
- Tae Hyung Kim
- Jung Hyun Yoon
- Han-Seung Shin
- Jaewon Lee
- Jee H. Jung
- Hyung Sik Kim
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Affiliations: Laboratory of Marine Natural Product, College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea, Laboratory of Molecular Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea, Department of Food Science and Biotechnology, Dongguk University-Seoul, Seoul 100-715, Republic of Korea
Published online on: September 17, 2014 https://doi.org/10.3892/ijo.2014.2659
Pages: 2331-2340

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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.

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