Sensitization of squamous cell carcinoma to cisplatin induced killing by natural agents.
Cisplatin resistance is a major problem in the successful treatment of squamous cell carcinoma (SCC). In the present study we showed, for the first time, that the constitutive activation of NF-kappaB partly contributes to cisplatin resistance and that the inactivation of NF-kappaB by natural agents [G2535 (isoflavone mixture containing genistein and diadzein), 3,3'-diindolylmethane (Bioresponse BR-DIM referred to as B-DIM)] could overcome this resistance, resulting in the inhibition of cell growth and induction of apoptosis, which might be an useful strategy for achieving better treatment outcome in patients diagnosed with cisplatin-resistant tumors of SCC.
Ali
Shadan
S
Division of Hematology/Oncology, Karmanos Cancer Center, Wayne State University, Detroit, MI, USA.
Varghese
Lalee
L
Department of Pathology, Karmanos Cancer Center, Wayne State University, Detroit, MI, USA.
Pereira
Lucio
L
Department of Otolaryngology, Karmanos Cancer Center, Wayne State University, Detroit, MI, USA.
Tulunay-Ugur
Ozlem E
OE
Department of Otolaryngology, Karmanos Cancer Center, Wayne State University, Detroit, MI, USA.
Kucuk
Omer
O
Division of Hematology/Oncology, Karmanos Cancer Center, Wayne State University, Detroit, MI, USA.
Carey
Thomas E
TE
Department of Otolaryngology, University of Michigan, Ann Arbor, MI, USA.
Wolf
Gregory T
GT
Department of Otolaryngology, University of Michigan, Ann Arbor, MI, USA.
Sarkar
Fazlul H
FH
Department of Pathology, Karmanos Cancer Center, Wayne State University, Detroit, MI, USA. Electronic address: fsarkar@med.wayne.edu.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D051034:Inhibitor of Apoptosis Proteins; D007529:Isoflavones / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D000077022:Survivin; D051020:bcl-X Protein / Q000235:genetics
D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; C107489:BIRC5 protein, human; D007211:Indoles; D051034:Inhibitor of Apoptosis Proteins; D007529:Isoflavones; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D051020:bcl-X Protein; C004742:daidzein; D004247:DNA; D019833:Genistein; D002945:Cisplatin; C016392:3,3'-diindolylmethane