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  3. Bergenin inhibits growth of human cervical cancer cells by decreasing Galectin-3 and MMP-9 expression

Bergenin inhibits growth of human cervical cancer cells by decreasing Galectin-3 and MMP-9 expression

  • Sci Rep. 2024 Jul 3;14(1):15287. doi: 10.1038/s41598-024-64781-3.
Ravi Chauhan 1,  Lakshay Malhotra 2 3,  Ashna Gupta 1,  Gunjan Dagar 1,  Mohini Mendiratta 4,  Tariq Masoodi 5,  Sheema Hashem 6,  Sara Al Marzooqi 7,  Dayasagar Das 8,  Shahab Uddin 9,  Abdul Samath Ethayathulla 2,  Muzafar A Macha 10,  Ammira Al-Shabeeb Akil 7,  Ranjit Kumar Sahoo 4,  Ekta Rai 11,  Ajaz A Bhat 7,  Mayank Singh 12
Affiliations

Affiliations

  • 1 Department of Medical Oncology (Lab.), Dr. BRAIRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India.
  • 2 Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.
  • 3 Department of Biochemistry, Sri Venkateswara College, University of Delhi, New Delhi, India.
  • 4 Department of Medical Oncology, Dr. BRAIRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
  • 5 Laboratory of Cancer Immunology and Genetics, Sidra Medicine, Doha, Qatar.
  • 6 Department of Human Genetics, Sidra Medicine, Doha, Qatar.
  • 7 Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar.
  • 8 Department of Medicine, NYU Langone Health, New York, 10016, USA.
  • 9 Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar.
  • 10 Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Pulwama, Jammu and Kashmir, India.
  • 11 School of Life Sciences Jawahar Lal Nehru University, New Delhi, India.
  • 12 Department of Medical Oncology (Lab.), Dr. BRAIRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India. mayank.osu@gmail.com.
PMID: 38961106 DOI: 10.1038/s41598-024-64781-3
Abstract

Cervical Cancer is still the leading cause of Cancer mortality worldwide even after introduction of vaccine against Human papillomavirus (HPV), due to low vaccine coverage, especially in the developing world. Cervical Cancer is primarily treated by Chemo/Radiotherapy, depending on the disease stage, with Carboplatin/Cisplatin-based drug regime. These drugs being non-specific, target rapidly dividing cells, including normal cells, so safer options are needed for lower off-target toxicity. Natural Products offer an attractive option compared to synthetic drugs due to their well-established safety profile and capacity to target multiple oncogenic hallmarks of Cancer like inflammation, angiogenesis, etc. In the current study, we investigated the effect of Bergenin (C-glycoside of 4-O-methylgallic acid), a natural polyphenol compound that is isolated from medicinal Plants such as Bergenia crassifolia, Caesalpinia digyna, and Flueggea leucopyrus. Bergenin has been shown to have anti-inflammatory, anti-ulcerogenic, and wound healing properties but its Anticancer potential has been realized only recently. We performed a proteomic analysis of cervical carcinoma cells treated with bergenin and found it to influence multiple hallmarks of cancers, including Apoptosis, angiogenesis, and tumor suppressor proteins. It was also involved in many different cellular processes unrelated to Cancer, as shown by our proteomic analysis. Further analysis showed bergenin to be a potent-angiogenic agent by reducing key angiogenic proteins like Galectin 3 and MMP-9 (Matrix Metalloprotease 9) in cervical carcinoma cells. Further understanding of this interaction was carried out using molecular docking analysis, which indicated MMP-9 has more affinity for bergenin as compared to Galectin-3. Cumulatively, our data provide novel insight into the anti-angiogenic mechanism of bergenin in cervical carcinoma cells by modulation of multiple angiogenic proteins like Galectin-3 and MMP-9 which warrant its further development as an Anticancer agent in cervical Cancer.

Keywords

Bergenin; Cervical cancer; Galectin 3; HPV; Matrix metallo protease 9.

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