J. Cancer Mol. 3: 121-128, 2007
and Quercetin Combined with Cisplatin to Induce Apoptosis in Human
Laryngeal Carcinoma Hep-2 Cells through the Mitochondrial Pathway
Meenakshi Kuhar, Sabiha Imran, and Neeta Singh
Biochemistry, All India Institute of Medical Sciences, New Delhi, India
Natural chemopreventives and antioxidants may modulate the response to
chemotherapy. In this study we have examined the chemoadjuvant
potential of curcumin and quercetin on cisplatin-mediated cell
killing/apoptosis, especially the role of mitochondria in the esophageal
cancer cell line Hep-2.
Apoptosis was detected by flow cytometry. The protein expression of
mitochondrion-related apoptotic mediators, i.e. Bcl-2, Bcl-XL,
Bax, cytochrome c, and AIF, were studied by Western Blotting.
The transcripts of anti-oxidant enzymes were quantitated by RT-PCR.
The findings suggest that priming Hep-2 cells with curcumin increased
the cisplatin-induced apoptosis by 7.1% whereas priming with quercetin
increased it by 16.3%. Curcumin induced apoptosis in Hep-2 cells, which
was mediated by an increase in Bax and nuclear AIF and a decrease in Bcl-XL.
Quercetin on the other hand, induced apoptosis through a
caspase-3-dependent pathway involving the participation of the proteins
Bcl-2, Bcl-XL, Bax and cytochrome c. The anti-oxidant
enzymes Mn-superoxide dismutase,
Cu-Zn superoxide dismutase, glutathione peroxidase, and catalase
did not show any significant increase at the transcriptional level in
case of combination of curcumin or quercetin with cisplatin.
The data suggests that priming with curcumin or quercetin may improve
the efficacy of chemotherapy for head and neck cancer by inducing
apoptosis through the mitochondrial pathway, thus minimizing the side
effects associated with combination chemotherapy.
Received 5/8/07; Revised 7/8/07; Accepted 7/18/07.
Dr. Neeta Singh,
Room No. 3027A, Department of Biochemistry, All India Institute of
Medical Sciences, New Delhi 1-110029, India. Phone: 91-11-26594945. Fax:
apoptosis-inducing factor; ROS, reactive oxygen species.
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