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PLGA-loaded Nedaplatin (PLGA-NDP) inhibits 7,12-Dimethylbenz[a]anthracene (DMBA) induced Oral carcinogenesis via modulating Notch signaling pathway and induces apoptosis in experimental hamster model
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  • Ilanchitchenni Senkuttuvan,
  • Suresh K.,
  • Theerthu Azhamuthu,
  • Nihal Ahamed Abulkalam Asath,
  • Pugazhendhi Ravichandran,
  • Rajeshwari Vasu
Ilanchitchenni Senkuttuvan
Annamalai University
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Suresh K.
Annamalai University

Corresponding Author:suraj_cks@yahoo.co.in

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Theerthu Azhamuthu
Annamalai University
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Nihal Ahamed Abulkalam Asath
Annamalai University
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Pugazhendhi Ravichandran
Annamalai University
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Rajeshwari Vasu
Annamalai University
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Abstract

The present study is designed to evaluate the nanotherapeutic efficacy of prepared PLGA-loaded Nedaplatin (PLGA-NDP) against 7,12-dimethyl benz(a)anthracene (DMBA)-induced experimental oral carcinogenesis in hamster buccal pouch (HBP) model. The buccal pouch of golden Syrian hamsters was painted with 0.5% DMBA in liquid paraffin three times a week for 14 weeks, ultimately leading to the development of oral squamous cell carcinoma (OSCC). Oral administration of PLGA-NDP (Pre-initiation) and Cisplatin delivery (5mg/kg b.wt) started one week before the carcinogen exposure and continued on alternative days. Post-administration of PLGA-NDP (5 mg/kg b.wt) started 2 days after carcinogen (DMBA) induction until the end of the experiment. After the 14 th week, we observed that DMBA-painted hamsters exhibited tumour formation, morphological alterations, and well-differentiated OSSC in addition to the responsive molecular proteins during oral carcinogenesis. Furthermore, immunoblotting analysis demonstrated that PLGA-NDP inhibits Notch signalling, as evidenced by downregulation of Bcl-Xl, Bcl-2, p21, PGE2, HGF, and CXCL12 proteins, and upregulation of p53 and Bax. This apoptotic response is crucial for PLGA-NDP to induce apoptosis. In addition, RT-PCR results showed that PLGA-NDP nanoparticles play a down-regulatory role in the therapeutic action of the notch signalling gene (Notch1, Notch 2, Hes1, Hey1, and Jagged1) at the mRNA transcription level in HBP carcinoma. Taken together, these data indicate that PLGA-NDP is a potent inhibitor of oral carcinogenesis and the expansion of cells that specifically target the Notch signalling pathway indicates that obstructing Notch signalling could potentially serve as a new and innovative therapeutic approach for oral squamous cell carcinoma (OSCC).
08 Jun 2024Submitted to Cell Biochemistry & Function
10 Jun 2024Submission Checks Completed
10 Jun 2024Assigned to Editor
10 Jun 2024Review(s) Completed, Editorial Evaluation Pending
11 Jun 2024Reviewer(s) Assigned
08 Jul 2024Editorial Decision: Revise Major
29 Aug 20241st Revision Received
29 Aug 2024Review(s) Completed, Editorial Evaluation Pending
29 Aug 2024Submission Checks Completed
29 Aug 2024Assigned to Editor
30 Aug 2024Reviewer(s) Assigned
25 Sep 2024Editorial Decision: Accept