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Molecular evidence of curcumin-induced apoptosis in the filarial worm Setaria cervi

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Abstract

Curcumin (diferuloyl methane) is a major curcuminoid from Curcuma longa that exhibits various pharmacological effects and has shown multiple beneficial activities. Our understanding of its anticarcinogenic and other activities occurring through curcumin-induced apoptosis in several cancer cells has greatly expanded in recent years. Lymphatic filariasis is a worldwide health problem causing global disability in humans and is caused by filarial nematodes. Development of efficient strategies to promote programmed cell death in filarial worms remains a key challenge for anti-filarial drug developing research and a crucial unmet medical need. In this study, we have taken molecular and biochemical approaches toward understanding the molecular basis for curcumin-mediated anti-filarial activity in the filarial nematode Setaria cervi. Results of MTT assay showed that curcumin causes a significant reduction in viability of Mf and adults and thus acts as a potent macro- and micro-filaricidal agent. Hoechst staining, TUNEL staining, showed several apoptotic nuclei in different parts of curcumin-treated adults. At 25 μM concentration it showed chromosomal DNA fragmentation in adult worms. Our results indicate that curcumin decreases protein and mRNA expression levels of anti-apoptotic gene ced-9 and enhances both the levels of pro-apoptotic genes ced-3 and ced-4 in a dose-dependent manner. All these observations ascertained the apoptogenicity of curcumin at a minimum concentration of 50 μM in this filarial worm. Furthermore, we showed that curcumin causes depletion of parasitic glutathione level, enhances the activities of glutathione S-transferase and superoxide dismutase and stimulates rapid generation of reactive oxygen species (ROS). Here, we present molecular evidence on curcumin-induced apoptosis in the filarial nematode S. cervi with probable involvement of ROS in a caspase-dependent manner.

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Acknowledgments

We thank the Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi for supporting this work by a grant (grant no. BT/PR8779/Med/14/1282/2007). The authors Ananya Nayak and Prajna Gayen were supported by a fellowship from the Council of Scientific and Industrial Research (CSIR), India. S.P.S.B. is a Professor of Parasitology at the Department of Zoology, Visva-Bharati University, Santiniketan, India.

Conflict of interest

The authors have nothing to disclose.

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Correspondence to Santi P. Sinha Babu.

Additional information

Ananya Nayak and Prajna Gayen contributed equally in this paper.

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Nayak, A., Gayen, P., Saini, P. et al. Molecular evidence of curcumin-induced apoptosis in the filarial worm Setaria cervi . Parasitol Res 111, 1173–1186 (2012). https://doi.org/10.1007/s00436-012-2948-0

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Keywords

  • Curcumin
  • Adult Worm
  • Lymphatic Filariasis
  • Curcumin Treatment
  • Filarial Nematode