Inhibition of cell cycle progression and induction of apoptosis in HeLa cells by HY558-1, a novel CDK inhibitor isolated from Penicillium minioluteum F558

Haeyoung Lim, Min Kyoung Kim, Youl Hee Cho, Jung Mogg Kim, Yoongho Lim, Chul Hoon Lee

Research output: Contribution to journalArticle

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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 p21WAF1/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 G1 phase arrest by inhibiting pRb phosphorylation via an upregulation of p21WAF1/CIP1, 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.

Original languageEnglish
Pages (from-to)978-984
Number of pages7
JournalJournal of Microbiology and Biotechnology
Volume14
Issue number5
StatePublished - 2004 Oct 1

Fingerprint

Penicillium
HeLa Cells
Cell Cycle
Apoptosis
Cyclin A
G2 Phase
Cell Division
Phosphorylation
G1 Phase Cell Cycle Checkpoints
Poly(ADP-ribose) Polymerases
G1 Phase
DNA Fragmentation
Cell Cycle Checkpoints
Cytochromes c
Caspase 3
Cytosol
Mitochondria
Adenocarcinoma
Up-Regulation
Western Blotting

Keywords

  • Apoptosis
  • Cell cycle arrest
  • HY558-1
  • Penicillium minioluteum F558

Cite this

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title = "Inhibition of cell cycle progression and induction of apoptosis in HeLa cells by HY558-1, a novel CDK inhibitor isolated from Penicillium minioluteum F558",
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 p21WAF1/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 G1 phase arrest by inhibiting pRb phosphorylation via an upregulation of p21WAF1/CIP1, 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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Inhibition of cell cycle progression and induction of apoptosis in HeLa cells by HY558-1, a novel CDK inhibitor isolated from Penicillium minioluteum F558. / Lim, Haeyoung; Kim, Min Kyoung; Cho, Youl Hee; Kim, Jung Mogg; Lim, Yoongho; Lee, Chul Hoon.

In: Journal of Microbiology and Biotechnology, Vol. 14, No. 5, 01.10.2004, p. 978-984.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Inhibition of cell cycle progression and induction of apoptosis in HeLa cells by HY558-1, a novel CDK inhibitor isolated from Penicillium minioluteum F558

AU - Lim, Haeyoung

AU - Kim, Min Kyoung

AU - Cho, Youl Hee

AU - Kim, Jung Mogg

AU - Lim, Yoongho

AU - Lee, Chul Hoon

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Y1 - 2004/10/1

N2 - 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 p21WAF1/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 G1 phase arrest by inhibiting pRb phosphorylation via an upregulation of p21WAF1/CIP1, 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.

AB - 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 p21WAF1/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 G1 phase arrest by inhibiting pRb phosphorylation via an upregulation of p21WAF1/CIP1, 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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