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Saha, Prosenjit
- Xanthone from Swertia chirata Exerts Chemotherapeutic Potential Against Colon Carcinoma
Abstract Views :178 |
PDF Views:77
Authors
Atish Barua
1,
Pritha Choudhury
1,
Niraj Nag
2,
Anirban Nath
3,
Sabyasachi Kundagrami
4,
Amit Pal
2,
Chinmay Kumar Panda
5,
Prosenjit Saha
1
Affiliations
1 Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, IN
2 Division of Pathophysiology, National Institute of Cholera and Enteric Diseases, P-33, CIT Road, Scheme-XM, Beliaghata, Kolkata 700 010, IN
3 Department of Genetics and Plant Breeding, University of Calcutta, Kolkata 700 073, IN
4 Department of Genetics and Plant Breeding, University of Calcutta, Kolkata 700 073, India, IN
5 Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, IN
1 Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, IN
2 Division of Pathophysiology, National Institute of Cholera and Enteric Diseases, P-33, CIT Road, Scheme-XM, Beliaghata, Kolkata 700 010, IN
3 Department of Genetics and Plant Breeding, University of Calcutta, Kolkata 700 073, IN
4 Department of Genetics and Plant Breeding, University of Calcutta, Kolkata 700 073, India, IN
5 Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, IN
Source
Current Science, Vol 122, No 1 (2022), Pagination: 47-55Abstract
The present study examines whether 1,5,8-tri-hydroxy-3-methoxy xanthone (TMX) isolated from Swertia chirata could restrict colon cancer cells by downregulating proliferation and inducing apoptosis. The chemotherapeutic activity of TMX was evaluated in several colon cancer and normal cell lines using in vitro assays like MTT assay, cell-cycle analysis, caspase-3 activity assay, annexin V/PI staining, JC10 assay, intracellular reactive oxygen species (ROS) level determination by dicholorofluorescein di-acetate (DCFH-DA). The present study revealed that TMX from S. chirata could effectively inhibit proliferation of metastatic colon cancer cell lines. The chemotherapeutic potential of TMX against metastatic colon cancer cell lines was achieved by downregulating several critical regulatory genes enabling the suppression of the proliferative potential of colon cancer cells and driving them towards apoptosis in a ROS dependent manner. In addition, TMX showed chemosensitization potential in colon cancer cell linesKeywords
Apoptosis, Chemosensitization, Colon Cancer, Reactive Oxygen Species, Swertia chirata.References
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- Evaluation of chemopreventive potential of xanthone from Swertia chirata against DMBA/croton oil-induced chemical carcinogenesis in Swiss mice
Abstract Views :200 |
PDF Views:91
Authors
Affiliations
1 Chittaranjan National Cancer Institute, Shyama Prasad Mukherjee Road, Bakul Bagan, Bhowanipore, Kolkata 700 026, IN
2 Chittaranjan National Cancer Institute, Shyama Prasad Mukherjee Road, Bakul Bagan, Bhowanipore, Kolkata 700 026, IN
1 Chittaranjan National Cancer Institute, Shyama Prasad Mukherjee Road, Bakul Bagan, Bhowanipore, Kolkata 700 026, IN
2 Chittaranjan National Cancer Institute, Shyama Prasad Mukherjee Road, Bakul Bagan, Bhowanipore, Kolkata 700 026, IN
Source
Current Science, Vol 122, No 4 (2022), Pagination: 429-438Abstract
The present study was designed to determine the chemopreventive efficiency of 1,5,8-trihydroxy-3-methoxy xanthone, abbreviated as TMX, isolated and purified from the aerial part of the plant Swertia chirata against 9,10-dimethylbenz[a]-anthracene (DMBA)/croton oil-induced skin cancer, and probe into the molecular mechanism. All the mice in the carcinogen control group developed severe dysplastic lesions after the 14th week of application of the carcinogen, which progressed to carcinoma in situ around the 20th week; this was validated histologically. However, after TMX treatment, only around 50% of mice developed papilloma which histologically was found to be restrictive to moderate to severe hyperplastic change in the 14th and 20th week. The chemopreventive potential was determined by calculating the attributable risk (AR), which was –11.3 for the 14th week and increased up to –17.5 for the 20th week. To ascertain the effect of TMX treatment on inflammation, the effect of TMX on inflammatory cytokines was studied by ELISA. It revealed a significant reduction in inflammation upon TMX treatment for the 20th week. As TMX could hold its chemopreventive potential up to the 20th week, the molecular mechanism of restriction was studied for the 20th week of treatment. Skin forms a rich source of stem cells which orchestrate the progression of carcinogenesis and become cancer stem cells (CSCs). β-Catenin and KRAS are known central modulators of CSCs, that play a crucial role in the progression of skin carcinogenesis. We observed that TMX treatment inhibited KRAS and nuclear translocation of β-catenin causing its cytoplasmic degradation by P-53 and P-21-mediated pathway, thereby exerting its chemopreventive potential.Keywords
Attributable risk, carcinogenesis, chemopreventive efficiency, mice, Swertia chirata, xanthone.References
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