Biological and chemical inhibitors of NF-κB sensitize SiHa cells to cisplatin-induced apoptosis

Manickam Venkatraman, Ruby John Anto, Asha Nair, Merina Varghese, Devarajan Karunagaran

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

Cisplatin, a chemotherapeutic agent, is known to induce apoptosis of cancer cells. We examined the role of NF-κB during cisplatin-induced apoptosis in two human cervical cancer cell lines, HeLa and SiHa, known to differ in their response to cisplatin treatment. We found that SiHa cells were relatively more resistant than HeLa cells to the cytotoxic effects induced by cisplatin as measured by MTT assays. HeLa cells were more sensitive to the apoptotic effects induced by cisplatin as shown by increases in annexin staining, DNA fragmentation, and loss of mitochondrial membrane potential. Similarly the activities of caspases 3, 8, and 9 and cleavage of PARP induced by cisplatin were more in HeLa than SiHa cells. Cisplatin induced NF-κB DNA binding activity in HeLa and SiHa cells but not in primary cervical cells and the active DNA binding complex in SiHa cells consists of p50 and RelA heterodimers. However, when NF-κB DNA binding activity was blocked by chemical (curcumin, PDTC, or salicylic acid) or biological inhibitors (NIK-KM or IKK-β DN), the cell viability was less in SiHa cells with cisplatin treatment, but these effects were not observed in HeLa cells. Similarly upon treatment with cisplatin SiHa cells had more activation of caspases compared to that seen in HeLa cells under conditions of NF-κB inhibition by biological or chemical inhibitors. These results suggest that NF-κB may contribute to the resistance of human cervical cancer cells to cisplatin and highlight the potential use of combination therapy involving cisplatin and NF-κB inhibitors.

Original languageEnglish
Pages (from-to)51-59
Number of pages9
JournalMolecular Carcinogenesis
Volume44
Issue number1
DOIs
StatePublished - Sep 2005
Externally publishedYes

Keywords

  • Apoptosis
  • Cisplatin
  • HeLa
  • NF-κB inhibitors
  • SiHa

Fingerprint

Dive into the research topics of 'Biological and chemical inhibitors of NF-κB sensitize SiHa cells to cisplatin-induced apoptosis'. Together they form a unique fingerprint.

Cite this