title: Molecular evidence of curcumin-induced apoptosis in the filarial worm Setaria cervi.
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.
authors.affiliation: Parasitology Laboratory, Department of Zoology, Visva-Bharati University, Santiniketan, 731 235, West Bengal, India.
authors.forename: Ananya
authors.initials: A
authors.lastname: Nayak
authors.forename: Prajna
authors.initials: P
authors.lastname: Gayen
authors.forename: Prasanta
authors.initials: P
authors.lastname: Saini
authors.forename: Niladri
authors.initials: N
authors.lastname: Mukherjee
authors.forename: Santi P Sinha
authors.initials: SP
authors.lastname: Babu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles; D003474:Curcumin / Q000494:pharmacology*; D018076:DNA, Complementary / Q000138:chemical synthesis; D018509:DNA, Helminth; D005260:Female; D020287:In Situ Nick-End Labeling; D008297:Male; D009348:Nematoda / Q000187:drug effects*; D018384:Oxidative Stress; D018510:RNA, Helminth; D017382:Reactive Oxygen Species; D013194:Staining and Labeling
chemical_list: D001562:Benzimidazoles; D018076:DNA, Complementary; D018509:DNA, Helminth; D018510:RNA, Helminth; D017382:Reactive Oxygen Species; D003474:Curcumin; C017807:bisbenzimide ethoxide trihydrochloride