Volume 41, Issue 1 pp. 185-197
ORIGINAL ARTICLE

Role and regulation of proapoptotic Bax in oral squamous cell carcinoma and drug resistance

Manzar Alam MSc

Manzar Alam MSc

Centre for Life Sciences, School of Natural Sciences, Central University of Jharkhand, Ranchi, Jharkhand, India

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Tanushree Kashyap MSc

Tanushree Kashyap MSc

Centre for Life Sciences, School of Natural Sciences, Central University of Jharkhand, Ranchi, Jharkhand, India

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Prajna Mishra MSc

Prajna Mishra MSc

Centre for Applied Chemistry, School of Natural Sciences, Central University of Jharkhand, Ranchi, Jharkhand, India

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Aditya K. Panda PhD

Aditya K. Panda PhD

Centre for Life Sciences, School of Natural Sciences, Central University of Jharkhand, Ranchi, Jharkhand, India

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Siddavaram Nagini PhD

Siddavaram Nagini PhD

Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, India

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Rajakishore Mishra PhD

Corresponding Author

Rajakishore Mishra PhD

Centre for Life Sciences, School of Natural Sciences, Central University of Jharkhand, Ranchi, Jharkhand, India

Correspondence

Rajakishore Mishra, Centre for Life Sciences, School of Natural Sciences, Central University of Jharkhand, Ratu-Lohardaga Road, Brambe, Ranchi-835205, Jharkhand, India.

Email: [email protected]; [email protected]

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First published: 14 December 2018
Citations: 45

Funding information: Department of Biotechnology, Ministry of Science and Technology, Grant/Award Number: BT/PR4624/MED/30/701/2012 BT/PR9028/INF/ 22/193/2013 (DBT BUILDER)

Abstract

Background

Bax, a proapoptotic protein but its regulation during oral cancer progression and resistance remains elusive.

Methods

A total of 127 samples including adjacent normal, primary tumor, and resistance to chemoradiation therapy (RCRT) samples from oral squamous cell carcinoma (OSCC) patients were used. The status of Bax was analyzed at DNA/mRNA/protein levels and the results were correlated with p53 and Akt expression in tissue samples/cisplatin-resistant oral tongue SCC (SCC9/SCC4-CisR) cell line.

Results

Frequent progressive decrease of Bax expression with infrequent promoter methylation, polymorphisms G(-248)A, and mutations was observed in OSCC progression/resistance. Furthermore, by targeting Akt pathway, induction of Bax-dependent cell death was observed and this was further enhanced with nimbolide treatment in SCC9/SCC4-CisR cells.

Conclusion

Hence, the Bax gene alteration and its deregulation through p53/Akt pathway are important for OSCC progression and drug resistance. Akt Inhibitor VIII and nimbolide synergistically induce Bax, and it is therefore beneficial for chemosensitizing cisplatin-resistant human OSCC.

CONFLICT OF INTEREST

The authors declare that they have no conflicts of interest with the contents of this article.

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