3.9 Article

Protective role of All Trans Retinoic Acid on B16F10 melanoma cell line metastasis in C57BL/6 mice by enhancing RAR- β protein and homeostasis maintenance

Journal

JOURNAL OF HISTOTECHNOLOGY
Volume 44, Issue 3, Pages 127-138

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/01478885.2021.1896291

Keywords

ATRA; metastasis; RAR-β C57BL; 6 mice; histopathology; immunohistochemistry; biochemistry

Categories

Funding

  1. Karunya Institute of Technology and Sciences through the Karunya Short Term Research Grant (KSTRG)
  2. Government of India agency, Department of Science and Technology, Science and Engineering Research Board (DST-SERB) [KITS/AR/OR/64/2017]
  3. Government of India agency, Department of Biotechnology (DBT), New Delhi, Karunya University [KITS/AR/OR/64/2017]
  4. DBT-EMR [BT/PR14632/NNT/28/824/2015]
  5. DST-SERB [SB/YS/LS-252/2013]

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All Trans Retinoic Acid (ATRA) has shown the ability to inhibit metastatic tumor growth in the lung and liver by inducing RAR-beta protein expression, leading to a reduction in pathological changes in these organs. ATRA also reduces cholesterol and GGT levels in cancer-induced mice, suggesting its potential as a therapeutic agent for lung cancer.
Lung cancer is the leading cancer according to the World Health Organization (WHO), resulting in highest death rate worldwide due to the high level of metastasis. Hence, the drugs that protect from metastasis either as an adjuvant or a primary therapeutic agent may help to reduce the death rate. In this study, All Trans Retinoic Acid (ATRA) was tested for its action against metastatic lodging of B16F10 melanoma cells in the lung and liver of the C57BL/6 mouse model. Serum, lung and liver were evaluated biochemically for the cancer associated changes. Metastatic cancer development was confirmed by tumor nodule formation and histopathological analysis. RAR-beta protein expression was analyzed by immunohistochemistry and histopathology. ATRA treated mice showed a percentage of inhibition on metastatic tumor growth in lung and liver and a corresponding protection against pathological changes in these organs. Cholesterol and gamma-Glutamyl Transferase (GGT) levels found in cancer induced mice were reduced in the ATRA treated group. As compared to the normal group, lung tissue from cell line induced cancer control group had less RAR-beta protein expression while the ATRA treated group showed enhanced RAR-beta protein expression. This indicates that the anti-metastasis effects of ATRA might have shown the induction of RAR-beta expression and subsequent molecular signaling pathways to regulate the homeostasis of biochemical changes. This study demonstrated the capability of ATRA to prevent the establishment of metastasis by the melanoma cell line into the lung and liver of experimental mice.

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