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Arsenic sulfide as a potential anti‑cancer drug.

Ding W, Zhang L, Kim S, Tian W, Tong Y, Liu J, Ma Y, Chen S - Mol Med Rep (2014)

Bottom Line: Arsenic sulfide (As4S4) is the main component of realgar, which is widely used in traditional Chinese medicine.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.These results suggest that As4S4 possesses potent in vitro and in vivo antitumor activity via the induction of cell apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.

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.

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Effect of As4S4 on the release of LDH and the activation of caspase-3 and −9. (A) Subsequent to exposure of A375 and MKN45 cells to the respective IC50s of As4S4 for 36 h, and exposure of L02 cells to 10 μg/ml As4S4, the leakage of LDH from cells was analyzed. (B) Caspase-3 and −9 activation was analyzed in MKN45 cells treated with different concentrations of As4S4 for 36 h: Control, 0 μg/ml; L, 0.25 × IC50; M, 0.5 × IC50 and H, 1 × IC50. Data are expressed as the mean ± standard deviation; *P<0.05, **P<0.01 and ***P<0.001 vs. control. As4S4, arsenic sulfide; LDH, lactate dehydrogenase; L, low; M, medium; H, high.
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f4-mmr-11-02-0968: Effect of As4S4 on the release of LDH and the activation of caspase-3 and −9. (A) Subsequent to exposure of A375 and MKN45 cells to the respective IC50s of As4S4 for 36 h, and exposure of L02 cells to 10 μg/ml As4S4, the leakage of LDH from cells was analyzed. (B) Caspase-3 and −9 activation was analyzed in MKN45 cells treated with different concentrations of As4S4 for 36 h: Control, 0 μg/ml; L, 0.25 × IC50; M, 0.5 × IC50 and H, 1 × IC50. Data are expressed as the mean ± standard deviation; *P<0.05, **P<0.01 and ***P<0.001 vs. control. As4S4, arsenic sulfide; LDH, lactate dehydrogenase; L, low; M, medium; H, high.

Mentions: The LDH release assay measured the leakage of LDH into the extracellular medium following cellular lysis. The release of intracellular LDH was detected following exposure to As4S4 (Fig. 4A). Meanwhile, caspase-3 and −9 were activated in MKN45 cells treated with As4S4 for 36 h (Fig. 4B). These results indicate the involvement of caspase-3 and −9 in As4S4-mediated cell apoptosis.


Arsenic sulfide as a potential anti‑cancer drug.

Ding W, Zhang L, Kim S, Tian W, Tong Y, Liu J, Ma Y, Chen S - Mol Med Rep (2014)

Effect of As4S4 on the release of LDH and the activation of caspase-3 and −9. (A) Subsequent to exposure of A375 and MKN45 cells to the respective IC50s of As4S4 for 36 h, and exposure of L02 cells to 10 μg/ml As4S4, the leakage of LDH from cells was analyzed. (B) Caspase-3 and −9 activation was analyzed in MKN45 cells treated with different concentrations of As4S4 for 36 h: Control, 0 μg/ml; L, 0.25 × IC50; M, 0.5 × IC50 and H, 1 × IC50. Data are expressed as the mean ± standard deviation; *P<0.05, **P<0.01 and ***P<0.001 vs. control. As4S4, arsenic sulfide; LDH, lactate dehydrogenase; L, low; M, medium; H, high.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4262477&req=5

f4-mmr-11-02-0968: Effect of As4S4 on the release of LDH and the activation of caspase-3 and −9. (A) Subsequent to exposure of A375 and MKN45 cells to the respective IC50s of As4S4 for 36 h, and exposure of L02 cells to 10 μg/ml As4S4, the leakage of LDH from cells was analyzed. (B) Caspase-3 and −9 activation was analyzed in MKN45 cells treated with different concentrations of As4S4 for 36 h: Control, 0 μg/ml; L, 0.25 × IC50; M, 0.5 × IC50 and H, 1 × IC50. Data are expressed as the mean ± standard deviation; *P<0.05, **P<0.01 and ***P<0.001 vs. control. As4S4, arsenic sulfide; LDH, lactate dehydrogenase; L, low; M, medium; H, high.
Mentions: The LDH release assay measured the leakage of LDH into the extracellular medium following cellular lysis. The release of intracellular LDH was detected following exposure to As4S4 (Fig. 4A). Meanwhile, caspase-3 and −9 were activated in MKN45 cells treated with As4S4 for 36 h (Fig. 4B). These results indicate the involvement of caspase-3 and −9 in As4S4-mediated cell apoptosis.

Bottom Line: Arsenic sulfide (As4S4) is the main component of realgar, which is widely used in traditional Chinese medicine.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.These results suggest that As4S4 possesses potent in vitro and in vivo antitumor activity via the induction of cell apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.

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.

Show MeSH
Related in: MedlinePlus