Synthesis, spectral characterization, crystal structure, cytotoxicity and apoptosis—Inducing activity of two derivatives of 2-hydroxy-1,4-naphthaquinone

Rani, P.R. Kavitha; Fernandez, Annette; Laila, Shiny P.; Arunkumar, B.; Sreelakshmi, C.; Vishnu, V S

doi:10.1016/j.pdpdt.2017.01.180

Cited by 6 publications

(1 citation statement)

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“…Among the 1,4-naphthoquinone compounds, plumbagin, mitomycin and shikonin have been used in the development of potent anti-cancer drugs (27). However, these compounds exhibit high levels of cytotoxicity and significant side effects, making their application as anti-cancer drugs in the clinical setting problematic (28). Therefore, our previous study used 1,4-naphthoquinone as a common compound to synthesize novel naphthoquinone derivatives, which indicated significantly improved cytotoxicity and increased anti-tumor activity in several types of cancer cells (29,30).…”

Section: Introductionmentioning

confidence: 99%

Novel 1,4‑naphthoquinone derivatives induce reactive oxygen species‑mediated apoptosis in liver cancer cells

et al. 2018

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Derivatives of 1,4-naphthoquinone have excellent anti-cancer effects, but their use has been greatly limited due to their serious side effects. To develop compounds with decreased side effects and improved anti-cancer activity, two novel types of 1,4-naphthoquinone derivatives, 2,3-dihydro-2,3-epoxy-2-propylsulfonyl-5,8-dimethoxy-1,4-naphthoquinone (EPDMNQ) and 2,3-dihydro-2,3-epoxy-2-nonylsulfonyl-5,8-dimethoxy-1,4-naphthoquinone (ENDMNQ) were synthesized and their anti-tumor activities were investigated. The effects of EPDMNQ and ENDMNQ on cell viability, apoptosis and accumulation of reactive oxygen species (ROS) in liver cancer cells were determined by MTT cell viability assay and flow cytometry. The expression levels of mitochondrial, mitogen activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling pathway-associated proteins in Hep3B liver cancer cells were analyzed by western blot analysis. The results demonstrated that EPDMNQ and ENDMNQ inhibited the proliferation of liver cancer Hep3B, HepG2, and Huh7 cell lines but not that of normal liver L-02, normal lung IMR-90 and stomach GES-1 cell lines. The number of apoptotic cells and ROS levels were significantly increased following treatment with EPDMNQ and ENDMNQ, and these effects were blocked by the ROS inhibitor N -acetyl-L-cysteine (NAC) in Hep3B cells. EPDMNQ and ENDMNQ induced apoptosis by upregulating the protein expression of p38 MAPK and c-Jun N-terminal kinase and downregulating extracellular signal-regulated kinase and STAT3; these effects were inhibited by NAC. The results of the present study demonstrated that EPDMNQ and ENDMNQ induced apoptosis through ROS-modulated MAPK and STAT3 signaling pathways in Hep3B cells. Therefore, these novel 1,4-naphthoquinone derivatives may be useful as anticancer agents for the treatment of liver cancer.

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