Arsenic in Cancer Treatment: Challenges for Application of Realgar Nanoparticles (A Minireview)

Abstract

While intensive efforts have been made for the treatment of cancer, this disease is still the second leading cause of death in many countries. Metastatic breast cancer, late-stage colon cancer, malignant melanoma, multiple myeloma, and other forms of cancer are still essentially incurable in most cases. Recent advances in genomic technologies have permitted the simultaneous evaluation of DNA sequence-based alterations together with copy number gains and losses. The requirement for a multi-targeting approach is the common theme that emerges from these studies. Therefore, the combination of new targeted biological and cytotoxic agents is currently under investigation in multimodal treatment regimens. Similarly, a combinational principle is applied in traditional Chinese medicine, as formulas consist of several types of medicinal herbs or minerals, in which one represents the principal component, and the others serve as adjuvant ones that assist the effects, or facilitate the delivery, of the principal component. In Western medicine, approximately 60 different arsenic preparations have been developed and used in pharmacological history. In traditional Chinese medicines, different forms of mineral arsenicals (orpiment—As2S3, realgar—As4S4, and arsenolite—arsenic trioxide, As2O3) are used, and realgar alone is included in 22 oral remedies that are recognized by the Chinese Pharmacopeia Committee (2005). It is known that a significant portion of some forms of mineral arsenicals is poorly absorbed into the body, and would be unavailable to cause systemic damage. This review primary focuses on the application of arsenic sulfide (realgar) for treatment of various forms of cancer in vitro and in vivo.

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

“…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).…”

“…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).…”

Innovative Application of Some Coordination Compounds of Arsenic and Stibium

“…It was established that during 720 hrs their water absorption ability was 0.01-0.03 %. Their testing on photochemical and thermal stability (in air, isothermal aging at 40°C and 60°), on action (on definite time) of "light-weather" (complex action of moisture and of air oxygen, of ultra-violet eradiation of sun or of "scattered" sunlight, CO 2 ) showed, that during 1200 hrs the initial expression, color, optical transparency and mechanical properties (homogeneity of the surface without formation of splits) of antibiocorrosive covers has not deteriorated.…”

“…1) [11]. Despite of the fact that for extraction of arsenic and its pr oducts from realgar (As 4 S 4 ) -auripigment (As 4 S 6 ) ore first of all it is necessary to burn concentrate in special furnace, so environment pollution with sulfur dioxide and aerosol containing 2-3 % of white arsenic cannot be eliminated [2], that in case of revival of corr esponding enterprise makes topical a manufacturing and putting into operation the catching devices with appropriate design.…”

Mechanochemically driven amorphization of nanostructurized arsenicals, the case of β-As4S4

“…Careful inspection with X-ray powder diffraction (XRPD) related to the first sharp diffraction peak (FSDP) revealed this amorphous phase as extension of MQ As-rich glass-forming structural motifs stretching beyond As 2 S 3 stoichiometry. Generation of amorphous phase in addition to parent crystalline compound, albeit not exactly defined, was also detected in high-temperature polymorph of tetraarsenic tetrasulfide b-As 4 S 4 after dry or wet MM, studied in view of promising anticancer activity [8][9][10][11][12]. Recently, the macroscopic evolution processes associated with intrinsic sub-nanometer free-volume voids were comprehensively studied in this b-As 4 S 4 polymorph subjected to high-energy MM, using different mathematical treatment procedures applied to reconstructed positron annihilation lifetime (PAL) spectra [12].…”