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Article: Doxorubicin-induced apoptosis and chemosensitivity in hepatoma cell lines

TitleDoxorubicin-induced apoptosis and chemosensitivity in hepatoma cell lines
Authors
Issue Date2002
PublisherSpringer. The Journal's web site is located at http://www.springer.com/medicine/oncology/journal/280
Citation
Cancer Chemotherapy And Pharmacology, 2002, v. 49 n. 1, p. 78-86 How to Cite?
AbstractPurpose: Doxorubicin (DOX) is a commonly used anticancer drug which causes DNA damage and kills cancer cells mainly by apoptosis. However, the process leading to killing of cancer cells and the molecular basis of resistance to DOX are not well understood. To evaluate the role of p53 and the cellular effects of DOX on hepatoma cell lines, we examined three hepatoma cell lines with different p53 status - Huh-7 (mutated p53), HepG2 (wild-type p53) and Hep3B (deleted p53). Methods: The chemosensitivity of the three hepatoma cell lines was assessed using the MTT assay, and cell cycle distribution was evaluated by flow cytometry. Western blotting and immunostaining were employed to examine the protein alterations in response to DOX treatment, and a DNA fragmentation assay was performed to detect apoptosis. Results: Of the three cell lines, HepG2 was found to be most resistant to DOX, followed by Hep3B, and Huh-7 was most sensitive to DOX treatment. HepG2 showed G1 arrest 24 h after drug administration and upregulation of p53 protein level in a time-dependent manner. In Hep3B cells (deleted p53), G2/M phase arrest was observed soon after drug administration, accompanied by induced apoptosis that was p53-independent. In Huh-7 cells (mutated p53), which were most sensitive to DOX, there was neither G1 nor G2 arrest, and the level of p53 mutated protein was downregulated after DOX treatment. MDM2 and p27 proteins were downregulated in all cell lines independently of p53 status. p21 was upregulated following p53 activation at low doses of DOX in HepG2 cells, but at higher doses, p21 was downregulated in Huh-7 and HepG2 cells. Conclusion: DOX confers different chemosensitivity on different hepatoma cell lines with different p53 status. The contrasting relationships between chemosensitivity and p53 status and expression suggest that DOX-induced apoptosis and cell death involve pathways that are independent of p53.
Persistent Identifierhttp://hdl.handle.net/10722/88577
ISSN
2015 Impact Factor: 2.824
2015 SCImago Journal Rankings: 1.283
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLee, Ten_HK
dc.contributor.authorLau, Ten_HK
dc.contributor.authorNg, Ien_HK
dc.date.accessioned2010-09-06T09:45:12Z-
dc.date.available2010-09-06T09:45:12Z-
dc.date.issued2002en_HK
dc.identifier.citationCancer Chemotherapy And Pharmacology, 2002, v. 49 n. 1, p. 78-86en_HK
dc.identifier.issn0344-5704en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88577-
dc.description.abstractPurpose: Doxorubicin (DOX) is a commonly used anticancer drug which causes DNA damage and kills cancer cells mainly by apoptosis. However, the process leading to killing of cancer cells and the molecular basis of resistance to DOX are not well understood. To evaluate the role of p53 and the cellular effects of DOX on hepatoma cell lines, we examined three hepatoma cell lines with different p53 status - Huh-7 (mutated p53), HepG2 (wild-type p53) and Hep3B (deleted p53). Methods: The chemosensitivity of the three hepatoma cell lines was assessed using the MTT assay, and cell cycle distribution was evaluated by flow cytometry. Western blotting and immunostaining were employed to examine the protein alterations in response to DOX treatment, and a DNA fragmentation assay was performed to detect apoptosis. Results: Of the three cell lines, HepG2 was found to be most resistant to DOX, followed by Hep3B, and Huh-7 was most sensitive to DOX treatment. HepG2 showed G1 arrest 24 h after drug administration and upregulation of p53 protein level in a time-dependent manner. In Hep3B cells (deleted p53), G2/M phase arrest was observed soon after drug administration, accompanied by induced apoptosis that was p53-independent. In Huh-7 cells (mutated p53), which were most sensitive to DOX, there was neither G1 nor G2 arrest, and the level of p53 mutated protein was downregulated after DOX treatment. MDM2 and p27 proteins were downregulated in all cell lines independently of p53 status. p21 was upregulated following p53 activation at low doses of DOX in HepG2 cells, but at higher doses, p21 was downregulated in Huh-7 and HepG2 cells. Conclusion: DOX confers different chemosensitivity on different hepatoma cell lines with different p53 status. The contrasting relationships between chemosensitivity and p53 status and expression suggest that DOX-induced apoptosis and cell death involve pathways that are independent of p53.en_HK
dc.languageengen_HK
dc.publisherSpringer. The Journal's web site is located at http://www.springer.com/medicine/oncology/journal/280en_HK
dc.relation.ispartofCancer Chemotherapy and Pharmacologyen_HK
dc.subject.meshAntibiotics, Antineoplastic - pharmacologyen_HK
dc.subject.meshApoptosis - drug effectsen_HK
dc.subject.meshBlotting, Westernen_HK
dc.subject.meshCarcinoma, Hepatocellular - pathologyen_HK
dc.subject.meshCell Cycle - drug effectsen_HK
dc.subject.meshCell Cycle Proteins - biosynthesisen_HK
dc.subject.meshDNA Damage - physiologyen_HK
dc.subject.meshDNA Fragmentation - drug effectsen_HK
dc.subject.meshDoxorubicin - pharmacologyen_HK
dc.subject.meshDrug Resistance, Neoplasmen_HK
dc.subject.meshHumansen_HK
dc.subject.meshImmunohistochemistryen_HK
dc.subject.meshTetrazolium Saltsen_HK
dc.subject.meshThiazolesen_HK
dc.subject.meshTumor Cells, Cultureden_HK
dc.subject.meshTumor Suppressor Protein p53 - genetics - metabolismen_HK
dc.titleDoxorubicin-induced apoptosis and chemosensitivity in hepatoma cell linesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0344-5704&volume=49&spage=78&epage=86&date=2002&atitle=Doxorubicin-induced+apoptosis+and+chemosensitivity+in+hepatoma+cell+linesen_HK
dc.identifier.emailLee, T:tkwlee@hkucc.hku.hken_HK
dc.identifier.emailNg, I:iolng@hkucc.hku.hken_HK
dc.identifier.authorityLee, T=rp00447en_HK
dc.identifier.authorityNg, I=rp00335en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s00280-001-0376-4en_HK
dc.identifier.pmid11855756-
dc.identifier.scopuseid_2-s2.0-0036137529en_HK
dc.identifier.hkuros66021en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036137529&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume49en_HK
dc.identifier.issue1en_HK
dc.identifier.spage78en_HK
dc.identifier.epage86en_HK
dc.identifier.isiWOS:000173856400009-
dc.publisher.placeGermanyen_HK

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