Inhibition of cell cycle progression and induction of apoptosis in HeLa cells by HY558-1, a novel CDK inhibitor isolated from Penicillium minioluteum F558
- Authors
- Lim, Haeyoung; Kim, Min Kyoung; Cho, Youl-Hee; Kim, Jung Mogg; Lim, Yoongho; Lee, Chul-Hoon
- Issue Date
- Oct-2004
- Publisher
- 한국미생물·생명공학회
- Keywords
- HY558-1; Penicillium minioluteum F558; cell cycle arrest; apoptosis
- Citation
- Journal of Microbiology and Biotechnology, v.14, no.5, pp 978 - 984
- Pages
- 7
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- Journal of Microbiology and Biotechnology
- Volume
- 14
- Number
- 5
- Start Page
- 978
- End Page
- 984
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/46555
- ISSN
- 1017-7825
1738-8872
- Abstract
- In the course of screening for a novel inhibitor of CDC2, HY558-1 was isolated from a culture broth of Penicillium minioluteum F558. Moreover, it was found that HY558-1 had an effect on both the cell cycle regulation and apoptosis of human cervical adenocarcinoma HeLa cells. A flow cytometric analysis of HeLa cells revealed appreciable cell cycle arrest at the G1 and G2/M phases following treatment with HY558-1. Furthermore, DNA fragmentation due to apoptosis was observed in HeLa cells treated with HY558-1. To obtain further information on the cell cycle arrest and apoptotic induction induced by HY558-1, the expression of certain cell cycle and apoptosis-associated proteins was examined using a Western blot analysis. The results revealed that HY558-1 inhibited the phosphorylation of pRb and decreased the expression levels of CDK2, CDC2, and cyclin A in the cell cycle progression. It was also shown that the level of p21(WAF1/CIP1) was increased in HeLa cells treated with 0.52 mM of HY558-1. Accordingly, HY558-1 was found to inhibit the proliferation of HeLa cells through the induction of G I phase arrest by inhibiting pRb phosphorylation via an upregulation of p21(WAP1/C1P1), and G2/M phase arrest by directly inhibiting CDC2 and cyclin A. Moreover, HeLa cells treated with 0.52 mM of HY558-1 exhibited apoptotic induction associated with the cleavage of Bid and release of cytochrome c from mitochondria into the cytosol. Subsequent investigation of the activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP) suggested that the mitochondrial pathway was primarily involved in the HY558-1-induced apoptosis in HeLa cells.
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