Understanding the anticancer potential of inhibitor of BCL2, disarib in oral cancer cells and its toxicological evaluation in rodents (Record no. 432899)
[ view plain ]
| 000 -LEADER | |
|---|---|
| fixed length control field | 03174nam a22002417a 4500 |
| 008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION | |
| fixed length control field | 241213b |||||||| |||| 00| 0 eng d |
| 041 ## - LANGUAGE CODE | |
| Language code of text/sound track or separate title | Eng. |
| 082 ## - DEWEY DECIMAL CLASSIFICATION NUMBER | |
| Classification number | 616.99 |
| Item number | SID |
| 100 ## - MAIN ENTRY--PERSONAL NAME | |
| Personal name | Siddiqua, Humaira |
| 245 ## - TITLE STATEMENT | |
| Title | Understanding the anticancer potential of inhibitor of BCL2, disarib in oral cancer cells and its toxicological evaluation in rodents |
| 260 ## - PUBLICATION, DISTRIBUTION, ETC. (IMPRINT) | |
| Place of publication, distribution, etc | Bangalore : |
| Name of publisher, distributor, etc | Indian Institute of Science, |
| Date of publication, distribution, etc | 2024. |
| 300 ## - PHYSICAL DESCRIPTION | |
| Extent | vi, 133p. : |
| Other physical details | ill. |
| Accompanying material | e-Thesis |
| 500 ## - GENERAL NOTE | |
| General note | Includes bibliographical references. |
| 502 ## - DISSERTATION NOTE | |
| Dissertation note | PhD;2024;Biochemistry. |
| 520 ## - SUMMARY, ETC. | |
| Summary, etc | Overexpression of BCL2 has been reported in several cancers, such as B-cell lymphomas, leukemias, colorectal adenocarcinoma, breast cancer, prostate cancer, and oral cancer, making it an excellent target for cancer treatment. We have identified a novel BCL2 inhibitor, Disarib, which primarily inhibits BCL2 by predominantly binding to its BH1 domain. Considering that Head and Neck cancer is the second most prevalent cancer in India with a high BCL2 expression, the anticancer potential of Disarib was explored in Head and Neck cancer. In the current study, we have evaluated through a series of in vitro efficacy and mechanistic studies, followed by in vivo efficacy assessments using Head and Neck xenograft mouse models, which revealed that Disarib administration can cause a significant reduction in the rate of tumor progression by killing the cancer cells via activation of the intrinsic pathway of apoptosis. Toxicological studies of Disarib, including the preclinical acute toxicity analysis of Disarib, revealed the safe use of Disarib for further evaluation. Evaluation of body weight, organ weight, food, and water consumption analysis, along with an evaluation of hematological parameters and kidney-liver function tests, following continuous 45 days of oral administration of Disarib showed no significant deviations when compared between the treated and the control group. Similarly, 90 days toxicity study revealed no observable toxicity in any of the parameters studied indicating the safer use of Disarib for long-term treatment. Hence, our results suggest no adverse preclinical observations in the toxicity profile of Disarib when administered orally in mice. Although Disarib has the potential to develop as an anticancer therapeutic drug, it is important to further derivatize it with better efficacy than Disarib. Therefore, we have derivatized and screened BCL2 inhibitors in BCL2 high and BCL2 low cell lines. Two compounds (DSR 43 and 4-O-CH 3 ), emerged with improved efficacy as compared to Disarib, encouraging further investigation for their potential. Taken together, our results suggest that Disarib has the potential to be developed as a cancer therapeutic against Head and Neck cancer. Besides, results of toxicity studies reveal no or limited toxicity against normal cells and may be safe to use for further preclinical studies in non-rodents. |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM | |
| Topical term or geographic name as entry element | Cancer Biology |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM | |
| Topical term or geographic name as entry element | BCL2 |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM | |
| Topical term or geographic name as entry element | Disarib |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM | |
| Topical term or geographic name as entry element | in vitro efficacy |
| 700 ## - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Advised by Raghavan, Sathees C |
| 856 ## - ELECTRONIC LOCATION AND ACCESS | |
| Uniform Resource Identifier | https://etd.iisc.ac.in/handle/2005/6720 |
| 942 ## - ADDED ENTRY ELEMENTS (KOHA) | |
| Koha item type | Thesis |
No items available.
