Dihydroartemisinin improves the efficiency of chemotherapeutics in lung carcinomas in vivo and inhibits murine Lewis lung carcinoma cell line growth in vitro

Zhou, Huijun; Zhang, Jiali; Li, Ao; Zeng, Wang; Lou, Xiang Yang

doi:10.1007/s00280-009-1129-z

Cited by 73 publications

(56 citation statements)

References 31 publications

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“…DHA was also able to inhibit ovarian cancer cell (HO8910PM) growth and metastasis, following ovarian orthotopic transplantation, in vivo, probably via inhibiting proliferation, which is supported by our findings in vitro, and also consistent with other reports in papilloma virusexpressing epithelial (28), lung cancer (29), pancreas cancer (30) and hepatoma (23) in vivo. The dosage of DHA from our current experiment is 50 mg/kg, which is about the mid-range of dosages used in the literature.…”

Section: Discussionsupporting

confidence: 81%

Dihydroartiminisin inhibits the growth and metastasis of epithelial ovarian cancer

Wu¹,

Hu²,

Li³

et al. 2011

Oncol Rep

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Abstract. Dihydroartiminisin (DHA), the active component of a Chinese herb (Artemisia annua), has been utilised as an anti-malarial drug since ancient China. DHA has also been shown to inhibit proliferation of cancer in vitro. However, the capacity of DHA to inhibit the development of ovarian cancer is still unclear. The adhesion, invasion, and migration of human ovarian cancer cell line (HO8910PM) was determined following DHA treatment in vitro, using Matrigel coated plate, transwell membrane chamber, and wound healing models, respectively. A mouse ovarian cancer model was established by orthotopic inoculation of HO8910PM cell line in nude mice. The growth and metastasis in vivo was determined 8 weeks post-implantation in response to DHA treatment. The expression of phosphorylated focal adhesion kinase (pFAK) and matrix metalloproteinases (MMP-2 and MMP-9) was evaluated using Western blotting. The expression of Von Willebrand factor (vWF) and infiltration of macrophages were determined, using immunohistochemistry. DHA inhibits ovarian cancer cell proliferation, adhesion, migration and invasion in vitro in a dose-dependent manner, consistent with decreased expression of pFAK and MMP-2, but not MMP-9. DHA inhibited metastasis significantly in vivo, associated with reduced vWF expression and macrophage infiltration. In conclusion, DHA inhibits the development of ovarian cancer, in part via down-regulating pFAK, MMP-2, vWF and macrophage infiltration.

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Section: Discussionsupporting

confidence: 81%

Dihydroartiminisin inhibits the growth and metastasis of epithelial ovarian cancer

Wu¹,

Hu²,

Li³

et al. 2011

Oncol Rep

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“…The high concentrations (≥10μM or 2.84μg/ml) are similar to those of in vitro anti-tumor and anti-angiogenic studies [36]. In animal models, the doses used as antitumour or antiangiogenic are 10-20 times higher than those as antimalarial [14,40].…”

Section: Discussionsupporting

confidence: 48%

Hypoxia modulates the effect of dihydroartemisinin on endothelial cells

D’Alessandro¹,

Basilico²,

Corbett³

et al. 2011

Biochemical Pharmacology

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Artemisinin derivatives, the current cornerstone of malaria treatment, possess also antiangiogenic and anti-tumor activity. Hypoxia plays a crucial role both in severe malaria (as a consequence of the cytoadherence of infected erythrocytes to the microvasculature) and in cancer (due to the restricted blood supply in the growing tumour mass). However, the consequences of hypoxia onto the effects of artemisinins is under-researched.This study aimed at assessing how the inhibition of microvascular endothelial cell (HMEC-1) growth induced by dihydroartemisinin (DHA, an antimalarial drug and the active metabolite of currently in-use artemisinins) is affected by oxygen tension.Low doses of DHA (achieved in the patients' plasma when treating malaria) were more inhibitory in hypoxia, whereas high doses (required for anti-angiogenic or anti-tumor activity) were more effective in normoxia. The peroxide bridge is essential for cellular toxicity (deoxyDHA was inactive). High doses of DHA caused HMEC-1 apoptosis and G2 cell cycle arrest. Effects were mediated by the generation of oxidative stress as demonstrated by DCF-DA fluorescence and membrane lipid peroxidation analysis.Overall, these results suggest that DHA inhibition of endothelial cell growth is related to the level of tissue oxygenation and drug concentration. This should be considered when studying both the effects of artemisinin derivatives as antimalarials and the potential therapeutic applications of these drugs as anti-tumor agents.

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“…cancer types [20,42]. Generally, combining artemisinins with other drugs have increased the anti-tumour effect; however, ART has been shown to hinder some treatments via up-regulation of calmodulin signalling [46].…”

Section: Combinations Involving Artemisinins Have Been Studied In Vitmentioning

confidence: 99%

“…However, care needs to be taken when choosing combinations to minimise undesired interactions. Evidence from other studies suggests that some artemisinins may potentiate other, more established treatments [40][41][42]. We therefore tested the ability of ART and ATM to sensitise HCT116, SW480 and MCF7 cells to OXP and GEM.…”

mentioning

confidence: 99%

In vitro study of the anti-cancer effects of artemisone alone or in combination with other chemotherapeutic agents

Gravett

Liu

Krishna

et al. 2010

Cancer Chemother Pharmacol

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Dihydroartemisinin improves the efficiency of chemotherapeutics in lung carcinomas in vivo and inhibits murine Lewis lung carcinoma cell line growth in vitro

Abstract: Dihydroartemisinin is a potent compound against LLC cell line in vitro. In vivo, the combination strategy of DHA and chemotherapeutics holds promise for the treatment of relatively large and rapidly growing lung cancers.

Cited by 73 publications

References 31 publications

Dihydroartiminisin inhibits the growth and metastasis of epithelial ovarian cancer

Dihydroartiminisin inhibits the growth and metastasis of epithelial ovarian cancer

Hypoxia modulates the effect of dihydroartemisinin on endothelial cells

In vitro study of the anti-cancer effects of artemisone alone or in combination with other chemotherapeutic agents

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