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

ABSTRACT

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-β 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 γ-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-β protein expression while the ATRA treated group showed enhanced RAR-β protein expression. This indicates that the anti-metastasis effects of ATRA might have shown the induction of RAR-β 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.

KEYWORDS:

• ATRA
• B16F10 Melanoma cells
• metastasis
• RAR-β
• C57BL/6 mice
• histopathology
• immunohistochemistry
• biochemistry

Acknowledgments

We acknowledge the technical assistance in histopathology and animal maintenance given by Mr. Jeyakumar and Mr. Robert.

Disclosure statement

The authors declare that they have no conflicts of interest.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

Funding for this project was provided by the Karunya Institute of Technology and Sciences through the Karunya Short Term Research Grant (KSTRG). The facilities were shared with the Cancer Research Laboratory established by us with financial support from Government of India agencies, Department of Science and Technology, Science and Engineering Research Board (DST-SERB) and Department of Biotechnology (DBT), New Delhi, Karunya University [KITS/AR/OR/64/2017]; DST-SERB [Ref: No.SB/YS/LS-252/2013, dated 15 May 2014]; DBT-EMR [Ref. No.: BT/PR14632/NNT/28/824/2015].