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Volume 26
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10.3390/ijms26073186
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Article

Investigation of Anti-Cancer Properties of Novel Curcuminoids in Leukemic Cells and Dalton Lymphoma Ascites Model

by
Vijayalakshmi Sudarshan
1,
P. Shyamjith
2,†,‡,
Sujeet Kumar
3,†,
Febina Ravindran
2,
Bibha Choudhary
2,* and
Subhas S. Karki
1,*
1
Department of Pharmaceutical Chemistry, Dr. Prabhakar B Kore Basic Science Research Centre, Off-Campus, KLE College of Pharmacy (A Constituent Unit of KAHER-Belagavi), Bengaluru 560010, India
2
Institute of Bioinformatics and Applied Biotechnology, Electronic City Phase 1, Bengaluru 560100, India
3
Department of Pharmaceutical Chemistry, NITTE College of Pharmaceutical Sciences (A Constituent College of Nitte Deemed to Be University, Mangaluru), Bengaluru, 560064, India
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
Manipal Academy of Higher Eduction, Manipal 576104, India.
Int. J. Mol. Sci. 2025, 26(7), 3186; https://doi.org/10.3390/ijms26073186
Submission received: 28 January 2025 / Revised: 24 March 2025 / Accepted: 26 March 2025 / Published: 29 March 2025
(This article belongs to the Collection Anticancer Drug Discovery and Development)
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Abstract

Leukemia, one of the major causes of cancer death, ranks 11th worldwide among cancer-related deaths. The current treatment of leukemia faces challenges recently due to a high burden of side effects. It is well established that curcumin has anticancer and tumor-suppressing activities in several cancers in addition to leukemia. Accordingly, 15 derivatives were designed and prepared to improve the shortcomings of curcumin, such as poor aqueous solubility, chemical instability, and low bioavailability. All 15 were evaluated for cytotoxicity against the leukemic cell line MOLT-4, which led to the prioritization and further evaluation of compound curcuminoid (2E,5E)-2,5-bis((3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)cyclopentan-1-one 5i. 5i. Compared to curcumin, 5i was significantly more effective in inducing mitochondrial dysfunction in MOLT-4 cells; hence increased ROS production and cytotoxicity. Treatment groups showed change in mitochondrial membrane potential by flow cytometry analysis. Moreover, tumor volume reduction observed with 5i treatment in Dalton’s Lymphoma model was accompanied with low toxicity. Intrinsic pathways of apoptosis was initiated by compound 5i that lowered Bcl-2 expression while augmenting cytochrome c, Bak and Bax levels both in vivo and in vitro. These results showcase the potent antiproliferative as well as cytotoxic effects of 5i at nanomolar doses against leukemia being at least 60 times more effective than curcumin.
Keywords: curcuminoids; leukaemia; cyclopentanone derivatives; monoketone; cytotoxicity; apoptosis curcuminoids; leukaemia; cyclopentanone derivatives; monoketone; cytotoxicity; apoptosis

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MDPI and ACS Style

Sudarshan, V.; Shyamjith, P.; Kumar, S.; Ravindran, F.; Choudhary, B.; Karki, S.S. Investigation of Anti-Cancer Properties of Novel Curcuminoids in Leukemic Cells and Dalton Lymphoma Ascites Model. Int. J. Mol. Sci. 2025, 26, 3186. https://doi.org/10.3390/ijms26073186

AMA Style

Sudarshan V, Shyamjith P, Kumar S, Ravindran F, Choudhary B, Karki SS. Investigation of Anti-Cancer Properties of Novel Curcuminoids in Leukemic Cells and Dalton Lymphoma Ascites Model. International Journal of Molecular Sciences. 2025; 26(7):3186. https://doi.org/10.3390/ijms26073186

Chicago/Turabian Style

Sudarshan, Vijayalakshmi, P. Shyamjith, Sujeet Kumar, Febina Ravindran, Bibha Choudhary, and Subhas S. Karki. 2025. "Investigation of Anti-Cancer Properties of Novel Curcuminoids in Leukemic Cells and Dalton Lymphoma Ascites Model" International Journal of Molecular Sciences 26, no. 7: 3186. https://doi.org/10.3390/ijms26073186

APA Style

Sudarshan, V., Shyamjith, P., Kumar, S., Ravindran, F., Choudhary, B., & Karki, S. S. (2025). Investigation of Anti-Cancer Properties of Novel Curcuminoids in Leukemic Cells and Dalton Lymphoma Ascites Model. International Journal of Molecular Sciences, 26(7), 3186. https://doi.org/10.3390/ijms26073186

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