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Regression of Dalton’s lymphoma in vivo via decline in lactate dehydrogenase and induction of apoptosis by a ruthenium(II)-complex containing 4-carboxy N-ethylbenzamide as ligand

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Summary

A novel ruthenium(II)-complex containing 4-carboxy N-ethylbenzamide (Ru(II)-CNEB) was found to interact with and inhibit M4-lactate dehydrogenase (M4-LDH), a tumor growth supportive enzyme, at the tissue level. The present article describes modulation of M4-LDH by this compound in a T-cell lymphoma (Dalton’s Lymphoma: DL) vis a vis regression of the tumor in vivo. The compound showed a dose dependent cytotoxicity to DL cells in vitro. When a non toxic dose (10 mg/kg bw i.p.) of Ru(II)-CNEB was administered to DL bearing mice, it also produced a significant decline in DL cell viability in vivo. The DL cells from Ru(II)-CNEB treated DL mice showed a significant decline in the level of M4-LDH with a concomitant release of this protein in the cell free ascitic fluid. A significant increase of nuclear DNA fragmentation in DL cells from Ru(II)-CNEB treated DL mice also coincided with the release of mitochondrial cytochrome c in those DL cells. Importantly, neither blood based biochemical markers of liver damage nor the normal patterns of LDH isozymes in other tissues were affected due to the treatment of DL mice with the compound. These results were also comparable with the effects of cisplatin (an anticancer drug) observed simultaneously on DL mice. The findings suggest that Ru(II)-CNEB is able to regress Dalton’s lymphoma in vivo via declining M4-LDH and inducing mitochondrial dysfunction–apoptosis pathway without producing any toxicity to the normal tissues.

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Acknowledgment

This work was financially supported by a project from Department of Biotechnology (DBT), Govt. of India, (BT/PR5910/BRB/10/406/2005) sanctioned jointly to LM and SKT. The authors are thankful to UGC Centre of Advanced Studies programme to Department of Zoology, BHU, for providing infrastructural facilities. The help extended by Mr. S. Bhattacharyya, Ms. S. Srivastav, and Ms. B. Mishra is also acknowledged.

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The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Biochemistry & Molecular Biology Laboratory, Centre of Advanced Studies in Zoology, Banaras Hindu University, Varanasi, 221005, India

    Raj K. Koiri, Surendra K. Trigun, Kiran Pandey & Deobrat Dixit

  2. Department of Chemistry, Banaras Hindu University, Varanasi, 221005, India

    Lallan Mishra & Santosh K. Dubey

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  1. Raj K. Koiri
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  2. Surendra K. Trigun
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Correspondence to Surendra K. Trigun.

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Koiri, R.K., Trigun, S.K., Mishra, L. et al. Regression of Dalton’s lymphoma in vivo via decline in lactate dehydrogenase and induction of apoptosis by a ruthenium(II)-complex containing 4-carboxy N-ethylbenzamide as ligand. Invest New Drugs 27, 503–516 (2009). https://doi.org/10.1007/s10637-008-9202-8

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