A novel function of emodin

Chang, Li-Ching; Sheu, Hamm Ming; Huang, Yu‐Sheng; Tsai, Tsung-Yu; Kuo, Kou‐Wha

doi:10.1016/s0006-2952(99)00075-1

Cited by 46 publications

(14 citation statements)

References 35 publications

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“…There is widespread consensus that activity results from intra-and inter-strand cross-links that bend and unwind DNA, resulting in attraction of certain proteins with resultant interference with excision repair and other vital DNA processes [120][121][122].…”

Section: Cis-ptmentioning

confidence: 99%

Mechanisms of Anti-Cancer Agents Emphasis on Oxidative Stress and Electron Transfer

Kovacic

Osuna²

2000

CPD

149

105

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A large body of evidence has accumulated indicating involvement of oxidative stress (OS) in the mode of action of various bioactive substances, including those of the immune system. The data for anticancer drugs (main and miscellaneous) are summarized herein. Although diverse origins pertain, reactive oxygen species (ROS) are frequently generated by redox cycling via electron transfer (ET) groups, such as quinones (or phenolic precursors), metal complexes (or complexors), aromatic nitro compounds (or reduced products) and conjugated imines (or iminium species). We believe it is not coincidental that these functionalities are frequently found in anticancer agents or their metabolites. Generally, the ET moieties display reduction potentials in the physiologically active range. Often ROS are also implicated in more traditional rationales, namely, enzyme inhibition, membrane or DNA insult, and interference with DNA or protein synthesis. A multi-faceted approach to mechanism appears to be the most logical. Significantly, the unifying theme of ET-OS also applies to other drug categories, as well as to toxins, carcinogens, hormones, and enzymes. Since this theoretical framework aids in our understanding of drug action, it can serve as a useful tool in the design of more active and safer pharmaceuticals.

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Section: Cis-ptmentioning

confidence: 99%

Mechanisms of Anti-Cancer Agents Emphasis on Oxidative Stress and Electron Transfer

Kovacic

Osuna²

2000

CPD

149

105

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“…Changes in DNA adducts were also examined at the 8-hour post-cisplatin exposure time-point to assess DNA repair, particularly since emodin has been reported to induce ERCC1 and increase DNA repair [36]. The results in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The inhibitor has also demonstrated an ability to preferentially repress transformation and growth of HER-2/neu-overexpressing breast tumor cells [10], and induce apoptosis in human hepatoma tumor cells [11]. In a separate study, however, emodin reduced the cytotoxic activity of cisplatin and ultraviolet radiation, in part by increasing the expression of ERCC1, a component of the nucleotide excision repair complex that repairs DNA lesions induced by cisplatin and UV [12]. Thus, under certain conditions, emodin protects cells from the apoptotic effects of antitumor agents.…”

Section: Introductionmentioning

confidence: 99%

Protein kinase inhibitors emodin and dichloro-ribofuranosylbenzimidazole modulate the cellular accumulation and cytotoxicity of cisplatin in a schedule-dependent manner

Kurokawa

Siddik

2009

Cancer Chemother Pharmacol

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Purpose Protein kinase inhibitors (PKI) have become prominent agents in cancer therapeutics. However, the specificity for target kinase inhibition can be poor and unwanted effects can emerge in combination regimens. The PKI emodin, for instance, can produce mixed results when combined with cisplatin, and we have sought a biochemical pharmacologic explanation for the negative cytotoxic effects. Methods Human ovraian A2780 tumor cells were exposed to the PKI emodin or dichloro-ribofuranosylbenzimidazole (DRB) with cisplatin using several schedules, and cytotoxicity determined by a growth inhibition assay. Intracellular platinum levels and DNA adducts were estimated by flameless atomic absorption spectrophotomotery. Results When A2780 cells were exposed first to emodin or DRB and then to cisplatin alone, the cytotoxic effects of cisplatin were significantly enhanced, whereas simultaneous exposure did not enhance the cytotoxicity, but instead inhibited it in the case of DRB. The increase in activity of cisplatin in the sequenced schedule was not due to increases in intracellular levels of cisplatin or DNA adducts, whereas the cytotoxic inhibition was related to a significant fall in both intracellular platinum levels and DNA adducts, which were ascribed to inhibition in cisplatin uptake. Knockdowm of hCtr1 (the human copper transporter 1) by siRNA abrogated this inhibition in cisplatin uptake. Conclusion The results demonstrate that co-exposure of tumor cells to emodin or DRB with cisplatin inhibits platinum drug uptake by impacting the hCtr1 transporter and, thereby, reduce the cytotoxicity of cisplatin. Based on our findings, scheduling of the PKI and the cytotoxic agent should be a major consideration in the clinical design of combination regimens.

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“…The most active emodin (3) has been reported to exhibit the anticancer effect by a nucleotide excision repair 15) and to be effective against mouse leukemia L1210. 16) Moreover, this compound inhibited the HER-2/neu tyrosine kinase activity to exhibit the antitumor effect against HER-2/neu-overexpressing breast cancer cell, 17) however, exerted no cytotoxicity against ovarian cancer cell.…”

Section: Resultsmentioning

confidence: 99%

Antimutagenicity and Cytotoxicity of the Constituents from the Aerial Parts of Rumex acetosa

Lee

Choi

Koo

et al. 2005

Biological & Pharmaceutical Bulletin

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Four anthraquinones isolated for the first time from the aerial parts of Rumex acetosa (Polygonaceae), a Korean and a Japanese medicinal plant, and two synthetic derivatives were examined for their cytotoxicities against five cultured human tumor cell lines, i.e. A549 (non-small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system) and HCY15 (colon), using the Sulfrhodamine-B method in vitro and antimutagenic activities by Ames test with Salmonella typhimurium TA98 and TA100 and SOS chromotest with E. coli PQ37. Among the tested compounds, emodin strongly inhibited the proliferation of each examined tumor cell line with IC 50 values ranged from 2.94 to 3.64 m mg/ml and showed potent antimutagenic activities with 71.5% and 53.3% at the concentration of 0.1 mg/plate against the mutagens, NPD and sodium azide, respectively. Its antigenotoxic activity was also very effective at the final concentration of 10 m mg/reaction tube against the mutagens, MNNG and NQO by SOS chromotest, reducing the induction factors by 19.6% and 43.5%, respectively. The structure-activity correlation study suggests that an additional OH group at C-6 position in the anthraquinone nucleus may play an important role for their cytotoxicities and an introduction of OH-or OCH 3 group at C-6 position is necessary for their antimutagenicities.

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A novel function of emodin

Cited by 46 publications

References 35 publications

Mechanisms of Anti-Cancer Agents Emphasis on Oxidative Stress and Electron Transfer

Mechanisms of Anti-Cancer Agents Emphasis on Oxidative Stress and Electron Transfer

Protein kinase inhibitors emodin and dichloro-ribofuranosylbenzimidazole modulate the cellular accumulation and cytotoxicity of cisplatin in a schedule-dependent manner

Antimutagenicity and Cytotoxicity of the Constituents from the Aerial Parts of Rumex acetosa

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