The medicinal use of realgar (As4S4) and its recent development as an anticancer agent

Wu, Jinzhu; Shao, Yanbin; Li, Jialiang; Chen, Gang; Ho, Paul C.

doi:10.1016/j.jep.2011.03.071

Cited by 98 publications

(75 citation statements)

References 36 publications

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“…Currently, the clinical application of realgar is not established due to its insolubility. 30 Recently, several types of realgar NPs have been developed, and more effective results have been achieved compared with crude realgar in antitumor studies. 13,31,32 It has been reported that realgar NP suspension prepared by "solvent relay" strategy induces both apoptosis and necrosis in leukemia cell lines K562 and HL-60.…”

Section: Discussionmentioning

confidence: 99%

Caveolin-1 contributes to realgar nanoparticle therapy in human chronic myelogenous leukemia K562 cells

Shi

Liu

et al. 2016

IJN

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Section: Discussionmentioning

confidence: 99%

Caveolin-1 contributes to realgar nanoparticle therapy in human chronic myelogenous leukemia K562 cells

Shi

Liu

et al. 2016

IJN

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“…In ancient China, realgar (called Xiong-Huang) was applied in the treatment of several diseases including headache, vertigo, sore throat, mouth ulcers, tongue ulcers, etc. 1,2 In recent years, the effects of realgar on the proliferation and apoptosis of human ovarian and cervical cancer cells, 3 human chronic myelogenous leukemia K562 cells, 4 and human promyelocytic leukemia HL-60 cells 5 have been reported. However, poor water solubility and the resultant poor bioavailability greatly hamper the clinical applications of realgar.…”

Section: Introductionmentioning

confidence: 99%

Apoptosis and necrosis induced by novel realgar quantum dots in human endometrial cancer cells via endoplasmic reticulum stress signaling pathway

Wang¹,

Liu²,

Gou³

et al. 2015

IJN

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Realgar (A S4 S 4 ) has been used in traditional medicines for malignancy, but the poor water solubility is still a major hindrance to its clinical use. Realgar quantum dots (RQDs) were therefore synthesized with improved water solubility and bioavailability. Human endometrial cancer JEC cells were exposed to various concentrations of RQDs to evaluate their anticancer effects and to explore mechanisms by the MTT assay, transmission electron microscopy (TEM), flow cytometry, real-time reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis. Results revealed that the highest photoluminescence quantum yield of the prepared RQDs was up to approximately 70%, with the average size of 5.48 nm. RQDs induced antipro-liferative activity against JEC cells in a concentration-dependent manner. In light microscopy and TEM examinations, RQDs induced vacuolization and endoplasmic reticulum (ER) dilation in JEC cells in a concentration-dependent manner. ER stress by RQDs were further confirmed by increased expression of GADD153 and GRP78 at both mRNA and protein levels. ER stress further led to JEC cell apoptosis and necrosis, as evidenced by flow cytometry and mitochondrial membrane potential detection. Our findings demonstrated that the newly synthesized RQDs were effective against human endometrial cancer cells. The underlying mechanism appears to be, at least partly, due to ER stress leading to apoptotic cell death and necrosis.

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“…Realgar and realgar nanoparticles have been demonstrated to inhibit the proliferation of several cancer cell lines, including hepatocellular HepG2 cells (3,15), and in clinical trials for HCC (2). To improve the bioavailability of realgar through smaller sizes would be an advantageous strategy against solid tumors (9,10). In this regard, RQDs with a size of ~6 nm were prepared by a chemical method and were revealed to be effective in inhibiting the uterine cervix U14 tumor xenografts without overt toxicity in tumor-bearing mice (17).…”

Section: Discussionmentioning

confidence: 99%

“…HepG2 cells through endoplasmic reticulum stress Arsenic compounds have also been investigated for their effects against solid tumors, including hepatocellular carcinoma (HCC), in animal models and in humans (3,9,16). Our recent study investigated the effects of RQDs in animal models and identified that RQDs can effectively inhibit the uterine cervix U14 tumor xenografts in tumor-bearing mice, without producing overt toxicity (17).…”

Section: Realgar Quantum Dots Induce Apoptosis and Necrosis Inmentioning

confidence: 99%

“…The poor solubility of realgar limits its clinical applications (9) and presents a major challenge in cancer chemotherapy (10). The realgar nanoparticles (11)(12)(13) and realgar bioleaching solution (14) are more effective compared to crude realgar in antitumor studies, indicative of smaller sizes of realgar being preferable to achieve a more efficient bioavailability (9). Thus, realgar quantum dots (RQDs; 5.48±1.09 nm) were prepared in our previous study using a modified method (15).…”

Section: Introductionmentioning

confidence: 99%

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Realgar quantum dots induce apoptosis and necrosis in HepG2 cells through endoplasmic reticulum stress

et al. 2015

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Abstract. Realgar (As 4 S 4 ) has been used in traditional Chinese medicines for treatment of malignancies. However, the poor water solubility of realgar limits its clinical application. To overcome this problem, realgar quantum dots (RQDs; 5.48±1.09 nm) were prepared by a photoluminescence method. The mean particle size was characterized by high-resolution transmission electron microscopy and scanning electron microscopy. Our recent studies revealed that the RQDs were effective against tumor growth in tumor-bearing mice without producing apparent toxicity. The present study investigated their anticancer effects and mechanisms in human hepatocellular carcinoma (HepG2) cells. The HepG2 cells and human normal liver (L02) cells were used to determine the cytotoxicity of RQDs. The portion of apoptotic and dead cells were measured by flow cytometry with Annexin V-fluorescein isothiocyanate/propidium iodide double staining. Apoptosis-related proteins and genes were examined by western blot analysis and reverse transcription-quantitative polymerase chain reaction, and the mitochondrial membrane potential was assayed by confocal microscope with JC-1 as a probe. RQDs exhibited cytotoxicity in a concentration-dependent manner and HepG2 cells were more sensitive compared with normal L02 cells. At 15 µg/ml, 20% of the cells were apoptotic, while 60% of the cells were necrotic at 30 µg/ml. The anti-apoptosis protein Bcl-2 was dose-dependently decreased, while pro-apoptotic protein Bax was increased. There was a loss of mitochondrial membrane potential and expression of the stress genes C/EBP-homologous protein 10 and glucose-regulated protein 78 was increased by RQDs. RQDs were effective in the inhibition of HepG2 cell proliferation and this effect was due to induction of apoptosis and necrosis through endoplasmic reticulum stress. IntroductionThe use of arsenic in China can be traced back thousands of years. Arsenic and arsenic salts, including orpiment, realgar and arsenolite, were fundamental ingredients in certain cancer treatments (1). The Fowler's solution (1% potassium arsenite) was used in the treatment of malignant diseases, such as leukemia and Hodgkin's disease, by numerous physicians in the 19-20th centuries (1). Arsenic trioxide (As 2 O 3 ) has emerged as the first-line therapy in the treatment of acute promyelocytic leukemia (APL); however, the toxicity hinders its clinical applications (2,3).Realgar contains >90% arsenic sulfide and is widely used externally and internally in a number of traditional medicine recipes in China (4). For example, realgar in combination with Indigo naturalis and Salvia miltiorrhiza is effective against APL (5), and targets RING-type E3 ligase c-CBL to induce degradation of BCR-Abl in chronic myelogenous leukemia (6). Realgar also enhances the antitumor effects of imatinib (7). Results from multicenter clinical trials using oral realgar formulations plus intravenous As 2 O 3 against hematological malignancy are promising (8).However, realgar is insoluble in water, resulting in poor ...

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The medicinal use of realgar (As4S4) and its recent development as an anticancer agent

Cited by 98 publications

References 36 publications

Caveolin-1 contributes to realgar nanoparticle therapy in human chronic myelogenous leukemia K562 cells

Caveolin-1 contributes to realgar nanoparticle therapy in human chronic myelogenous leukemia K562 cells

Apoptosis and necrosis induced by novel realgar quantum dots in human endometrial cancer cells via endoplasmic reticulum stress signaling pathway

Realgar quantum dots induce apoptosis and necrosis in HepG2 cells through endoplasmic reticulum stress

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