IngentaConnect Novel anticancer agent, benzyldihydroxyoctenone, isolated from St...

Authors: Lee, Chul-Hoon; Lim, Haeyoung; Moon, Sangik¹; Shin, Choonshik¹; Kim, Seunghyun¹; Kim, Bum-Joon²; Lim, Yoongho

Source: Cancer Science, Volume 98, Number 6, June 2007 , pp. 795-802(8)

Publisher: Blackwell Publishing

Abstract:

In the course of screening for anticancer agents, a novel active compound, F3-2-5, was isolated from culture broth of Streptomyces sp., KACC91015. Its structure was identified using nuclear magnetic resonance, mass spectrometry, and molecular modeling experiments, and confirmed by total synthesis. The growth of various human cancer cell lines was inhibited in a dose-dependent manner by 0.06-0.48 mM F3-2-5 over 24 h. Its IC₅₀ values were estimated at 37 µM on HeLa, 72 µM on A549, and 190 µM on HT-29 cells. However, F3-2-5 had no antiproliferative effect on normal lymphocytes and normal fibroblasts used as controls. Moreover, it affected cell cycle regulation and caused apoptosis of the HeLa cells; chromatin condensation and DNA fragmentation were observed in cells exposed to 80 µM F3-2-5. Western blot analysis revealed that F3-2-5 inhibited phosphorylation of retinoblastoma protein (pRb) and reduced expression of cyclin-dependent kinase-4 and -6, and cyclin D1 and E, while levels of p53 and p21^WAF1/CIP1 increased. Taken together, these findings show that F3-2-5 inhibits proliferation of HeLa cells by inducing G₁ phase arrest as a consequence of inhibition of pRb phosphorylation following up-regulation of p21^WAF1/CIP1 and p53. Furthermore, apoptosis in HeLa cells treated with F3-2-5 was associated with an increase in Bax and p53, leading to release of cytochrome c, activation of caspase-3, and -8, and cleavage of poly (ADP-ribose) polymerase. (Cancer Sci 2007; 98: 795-802)

Document Type: Research article

DOI: 10.1111/j.1349-7006.2007.00473.x

Affiliations: 1: Bio/Molecular Informatics Center, Department of Bioscience and Biotechnology, IBST, Konkuk University, Seoul 143-701; 2: Department of Microbiology and Cancer Research Institute, Seoul National University, College of Medicine, Seoul 110-744, Korea

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Novel anticancer agent, benzyldihydroxyoctenone, isolated from Streptomyces sp. causes G1 cell cycle arrest and induces apoptosis of HeLa cells

Novel anticancer agent, benzyldihydroxyoctenone, isolated from Streptomyces sp. causes G₁ cell cycle arrest and induces apoptosis of HeLa cells