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Nimbolide retards T cell lymphoma progression by altering apoptosis, glucose metabolism, pH regulation, and ROS homeostasis.
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- Author(s): Jaiswara, Pradip Kumar1 (AUTHOR); Kumar, Ajay1 (AUTHOR)
- Source:
Environmental Toxicology. Jun2022, Vol. 37 Issue 6, p1445-1457. 13p.- Subject Terms:
- Source:
- Additional Information
- Abstract: Nimbolide is reported as one of the potential anticancer candidates of the neem tree (Azadirachta indica A. Juss). The cytotoxic action of nimbolide has been well reported against a wide number of malignancies, including breast, prostate, lung, liver, and cervix cancers. Interestingly, only a few in vivo studies conducted on B cell lymphoma, glioblastoma, pancreatic cancer, and buccal pouch carcinoma have shown the in vivo antitumor efficacy of nimbolide. Therefore, it is highly needed to examine the in vivo antineoplastic activity of nimbolide on a wide variety of cancers to establish nimbolide as a promising anticancer drug. In the present study, we investigated the tumor retarding action of nimbolide in a murine model of T cell lymphoma. We noticed significantly augmented apoptosis in nimbolide‐ administered tumor‐bearing mice, possibly due to down‐regulated expression of Bcl2 and up‐regulated expression of p53, cleaved caspase‐3, Cyt c, and ROS. The nimbolide treatment‐induced ROS production by suppressing the expression of antioxidant regulatory enzymes, namely superoxide dismutase and catalase. In addition, nimbolide administration impaired glycolysis and pH homeostasis with concomitant inhibition of crucial glycolysis and pH regulatory molecules such as GLUT3, LDHA, MCT1, and V‐ATPase, CAIX and NHE1, respectively. Taken together, the present investigation provides novel insights into molecular mechanisms of nimbolide inhibited T cell lymphoma progression and directs the utility of nimbolide as a potential anticancer therapeutic drug for the treatment of T cell lymphoma. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of Environmental Toxicology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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