Athira, Shaji (2019) In-Vitro Investigation of Metformin in Combination with Mannose as an Adjuvant Therapy for Breast Cancer Treatment. Masters thesis, PSG College of Pharmacy, Coimbatore.
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Abstract
Discovery of new drugs for cancer treatment is an expensive and time-consuming process and the percentage of drugs reaching the clinic remains quite less. Drug repositioning refers to the identification and development of new uses for existing drugs and represents an alternative drug development strategy.In oncology there is an increasing interest in the use of non-cancer drugs for cancer treatmens due to the previous detailed knowledge of pharmacokinetics/dynamics and toxicities, and because most repositioned drugs are available at low cost, normally as generics which provides an opportunity to bypass partially the early costs and time associated to new drugs development .The antitumour activity of Metformin appears to be valuable as an effective strategy for the treatment of all inoperable, chemotherapy-resistant or recurring breast cancers. Mannose represents an attractive option since it targets the key source of cellular energy in the breast cancer cells may represent a major advantage over classic chemotherapies. In our study we found that the co-treatment of Metformin and Mannose shows significant increase in growth inhibitory activity in MDA-MB 231 cell lines using MTT assay.The apoptosis of TNBC cells induced by Metformin and Mannose via increase of upregulation of caspase-3, caspase-8 and procaspase-9, which may be associated with both extrinsic & intrinsic mitochondrial pathway. We compared the motility of the Metformin treated cells and the combination of Mannose in MDA MB-231 cells using Wound healing assays. The percentage of wound closure was significantly decreased in Metformin & Mannose treated cells compared to that of Metformin alone treated cells. These results suggest that Metformin& Mannose combination have association EMT process reversal indicating less motility of the cells thus reducing the risk of distant metastatis. Gene expression studies should be done for further confirmation. Mitochondrial Membrane Potential (ΔΨm) is critical for maintaining the physiological function of the respiratory chain to generate ATP; the opening the mitochondrial permeability transition pore (MPTP) leads to the collapse of the ΔΨm and subsequent release of cytochrome C into the cytosol. We assessed the mitochondrial membrane potential using Rhodamine 123 staining showed that there was a reduction in flouresence intensity ie Mitochondrial Membrane Potential (ΔΨm) in treated group than the untreated and thus confirmed apoptotic activity was more in Metformin and Mannose treated groups. Reactive Oxygen specices was found to be more prominent in treated cells when compared to untreated using DCF-DA staining method. Apoptosis was confirmed by Ethidium Bromide and Acridine Orange staining assay. In conclusion, the present study demonstrated that the combination of Metformin and Mannose enhance the antiproliferative activity on MDA-MB 231cells via the intrinsic and extrinsic apoptotic pathways, indicated by Caspase assay. These findings suggested that Metformin and Mannose combination as adjuvant therapy may be a beneficial option to enhance the current chemotherapy in breast cancer .
| Item Type: | Thesis (Masters) |
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| Additional Information: | 261725908 |
| Uncontrolled Keywords: | In-Vitro Investigation of Metformin in Combination with Mannose as an Adjuvant Therapy for Breast Cancer Treatment |
| Subjects: | PHARMACY > Pharmacology |
| Depositing User: | Ramakrishnan J |
| Date Deposited: | 04 May 2022 09:05 |
| Last Modified: | 04 May 2022 09:05 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/19653 |
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