Nimbolide induces cell death in T lymphoma cells: Implication of altered apoptosis and glucose metabolism
| Autor: | Pratishtha Sonker, Rajan Kumar Tiwari, Shiv Govind Rawat, Ajay Kumar, Chandramani Pathak, Vishal Gupta, Pradip Kumar Jaiswara, Santosh Kumar |
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| Rok vydání: | 2020 |
| Předmět: |
Limonins
Programmed cell death Cell Survival Health Toxicology and Mutagenesis Cell Culture Techniques Caspase 3 Apoptosis 010501 environmental sciences Management Monitoring Policy and Law Toxicology Lymphoma T-Cell 01 natural sciences 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Cytotoxic T cell T-cell lymphoma Humans 0105 earth and related environmental sciences Cell Proliferation Cell growth Chemistry General Medicine medicine.disease Antineoplastic Agents Phytogenic Glucose Cell culture 030220 oncology & carcinogenesis Cancer cell Cancer research Reactive Oxygen Species |
| Zdroj: | Environmental toxicologyREFERENCES. 36(4) |
| ISSN: | 1522-7278 |
| Popis: | Nimbolide is a tetranortriterpenoid derived from the leaves and flowers of Azadirachta indica (Neem). It exhibits anticancer activity against a variety of cancers by modulating various crucial features, including cell proliferation, apoptosis, and invasion and metastasis. More importantly, the cytotoxic effect of nimbolide has also been observed against T cell lymphoma, but the underlying mechanisms are still unexplored. So far, no study has been conducted to observe the effect of nimbolide on cancer cell metabolism. Therefore, the present investigation was designed to explore the molecular mechanisms of the antitumor potential of nimbolide against T cell lymphoma, a neoplastic disorder of thymic origin. In addition, we also unraveled the anti-glycolytic activity of nimbolide against T lymphoma cells with possible molecular mechanisms. Our results showed the cytotoxic action of nimbolide against three different cell lines of T cell lymphoma, namely Dalton's lymphoma, HuT-78, and J6. Nimbolide-induced apoptosis in T lymphoma cells by altering the level of reactive oxygen species, p53, Bcl2, Bax, and cytochrome c, with subsequent cleavage of caspase 3. Remarkably, nimbolide inhibited the expression of hypoxia-inducible factor-1α, glucose transporter 3, hexokinase II, and pyruvate dehydrogenase kinase 1, which led to the suppression of glycolysis with concomitant activation of oxidative phosphorylation. Hence, the results of the present investigation demonstrate that nimbolide exerts tumoricidal activity against T lymphoma cells via augmentation of apoptosis and reversal of altered cell metabolism. Thus, the present study provides a new insight for the therapeutic utilization of nimbolide against T cell lymphoma. |
| Databáze: | OpenAIRE |
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