Juglone, a naphthoquinone from walnut, exerts cytotoxic and genotoxic effects against cultured melanoma tumor cells

Cell Biology International - Tập 33 - Trang 1039-1049 - 2009
B. Kiran Aithal1, M.R. Sunil Kumar1, B. Nageshwar Rao1, Nayanabhirama Udupa2, B.S. Satish Rao1
1Division of Radiobiology and Toxicology, Manipal Life Sciences Centre, Manipal University, Manipal 576104, Karnataka, India
2Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, India

Tóm tắt

AbstractThis study demonstrates cytotoxic and genotoxic potential of juglone, a chief constituent of walnut, and its underlying mechanisms against melanoma cells. MTT assay and clonogenic assay were used to study cytotoxicity, micronucleus assay to assess genotoxicity, glutathione (GSH) assay and 2′,7′‐dicholorofluorescein diacetate (DCFH‐DA) assay to evaluate the oxidative stress induction. Apoptosis/necrosis induction was analysed by flow cytometry. We observed a concentration‐dependent decrease in cell survival with a corresponding increase in the lactate dehydrogenase levels. A dose‐dependent increase in the frequency of micronucleated binucleate cells indicated the potential of juglone to induce cytogenetic damage in melanoma tumor cells. Moreover, results of the micronuclei study indicated division delay in the proliferating cell population by showing decrease in the cytokinesis blocked proliferation index. Further, juglone‐induced apoptosis and necrosis could be demonstrated by oligonucleosomal ladder formation, microscopic analysis, increase in the hypodiploid fraction (sub Go peak in DNA histogram), as well as an increased percentage of AnnexinV(+)/PI(+) cells detected by flow cytometry. A significant concentration‐dependent decrease in the glutathione levels and increase in dichlorofluorescein (DCF) fluorescence after juglone treatment confirmed the ability of juglone to generate intracellular reactive oxygen species. The cytotoxic effect of juglone can be attributed to mechanisms including the induction of oxidative stress, cell membrane damage, and a clastogenic action leading to cell death by both apoptosis and necrosis.

Tài liệu tham khảo

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Cell Biology International

Tập 33

1039-1049

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