title: Arsenic sulfide as a potential anti‑cancer drug.
abstract: Arsenic sulfide (As4S4) is the main component of realgar, which is widely used in traditional Chinese medicine. Previous studies have shown the beneficial effects of As4S4 in the treatment of hematological malignant diseases, however, its effects on solid tumors have yet to be fully elucidated. The current study aimed to explore the anti‑cancer effect and the mechanism of As4S4 on solid tumors in vitro and in vivo. Cells from four human solid tumor cell lines, including the MKN45 gastric cancer cell line, the A375 malignant melanoma cell line, the 8898 pancreatic carcinoma cell line and the HepG2 hepatocellular carcinoma cell line, were treated with As4S4 in vitro, using the L02 embryonic liver cells as a control. The efficacy of As4S4 was assessed in vivo using mice implanted with Lewis lung carcinoma cells. The results of the current study demonstrated that As4S4 significantly inhibited the proliferation of solid tumor cells in a dose‑ and time‑dependent manner, but produced a less pronounced effect on L02 cells. Additionally, As4S4 was observed to induce apoptosis (including morphological changes and an enhanced sub‑G1 population), which was accompanied by the activation of caspase‑3 and ‑9. Furthermore, treatment with As4S4 significantly inhibited the growth of implanted tumors in mice. These results suggest that As4S4 possesses potent in vitro and in vivo antitumor activity via the induction of cell apoptosis.
authors.affiliation: Department of Oncology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Wenping
authors.initials: W
authors.lastname: Ding
authors.affiliation: Department of Oncology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Lian
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Sungkyoung
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Oncology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tian
authors.affiliation: Department of Oncology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Tong
authors.affiliation: State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, P.R. China.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Shanghai Third People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201999, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Oncology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Siyu
authors.initials: S
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001152:Arsenicals / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D006836:Hydro-Lyases / Q000378:metabolism; D007376:Interleukin-2 / Q000097:blood; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D013440:Sulfides / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D007376:Interleukin-2; D013440:Sulfides; C045816:arsenic trisulfide; C058317:arsenic disulfide; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D006836:Hydro-Lyases; C045581:lactate dehydratase