Exploring anticancer potential of betanin in DMBA-induced oral squamous cell carcinoma: an in silico and experimental

Ramachandhiran Duraisamy1, Vinothkumar Veerasamy2, Vaitheeswari Balakrishnan1

  • 1Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Chidambaram, Annamalainagar, 608002, Tamil Nadu, India.

Insights

Betanin (BTN) demonstrates significant anticancer properties by protecting against 7,12-Dimethylbenz[a]anthracene (DMBA)-induced oral cancer in hamsters. This natural antioxidant restores key enzyme activities and inhibits tumor development, showing dose-dependent efficacy.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Oncology

Background:

  • Betanin (BTN) possesses antioxidant and radical scavenging properties.
  • 7,12-Dimethylbenz[a]anthracene (DMBA) exposure can lead to impaired xenobiotic metabolism and lipid peroxidation, contributing to cancer development.
  • Oral squamous cell carcinoma (OSCC) is a significant health concern, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To investigate the protective effects of betanin against DMBA-induced oral cancer in a hamster model.
  • To evaluate the impact of betanin on oxidative stress markers, xenobiotic enzyme activity, and tumor progression.
  • To explore the molecular mechanisms underlying betanin's anticancer activity through in silico analysis.

Main Methods:

  • Induction of oral cancer in hamsters using DMBA.
  • Administration of varying dosages of betanin (10, 20, 40 mg/kg b.w.) via intragastric intubation.
  • Assessment of tumor incidence, volume, burden, body weight, lipid peroxidation, and antioxidant enzyme activities.
  • Histopathological examination of oral tissues.
  • Molecular docking studies to assess binding affinities with key cancer-related proteins.

Main Results:

  • DMBA induction resulted in 100% tumor incidence, increased tumor burden, and elevated lipid peroxidation, alongside diminished antioxidant activity.
  • Betanin treatment significantly restored antioxidant levels, xenobiotic enzyme activity, and inhibited lipid peroxidation in a dose-dependent manner.
  • Histopathology confirmed betanin's ability to mitigate hyperkeratosis, hyperplasia, dysplasia, and OSCC progression.
  • Molecular docking revealed high binding affinity of betanin to crucial proteins involved in apoptosis and cell signaling pathways (Bax, Caspases, PI3K/AKT, p53, SMADs, TGF-β).

Conclusions:

  • Betanin exhibits prominent anticancer activity against DMBA-induced oral cancer.
  • The protective effects are attributed to the restoration of antioxidant defense systems and modulation of xenobiotic metabolism.
  • In vivo and in silico findings support betanin as a potential therapeutic agent for oral cancer treatment.

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