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Dihydroartemisinin induces apoptosis and sensitizes human ovarian cancer cells to carboplatin therapy.

Chen T, Li M, Zhang R, Wang H - J. Cell. Mol. Med. (2008)

Bottom Line: The in vitro and in vivo antitumour effects and possible underlying mechanisms of action of dihydroartemisinin (DHA), the most effective compound, were further determined in ovarian cancer cells.These effects were also observed in in vivo ovarian A2780 and OVCAR-3 xenograft tumour models.In conclusion, ARS derivatives, particularly DHA, exhibit significant anticancer activity against ovarian cancer cells in vitro and in vivo, with minimal toxicity to non-tumourigenic human OSE cells, indicating that they may be promising therapeutic agents for ovarian cancer, either used alone or in combination with conventional chemotherapy.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, PR China.

ABSTRACT
The present study was designed to determine the effects of artemisinin (ARS) and its derivatives on human ovarian cancer cells, to evaluate their potential as novel chemotherapeutic agents used alone or in combination with a conventional cancer chemotherapeutic agent, and to investigate their underlying mechanisms of action. Human ovarian cancer cells (A2780 and OVCAR-3), and immortalized non-tumourigenic human ovarian surface epithelial cells (IOSE144), were exposed to four ARS compounds for cytotoxicity testing. The in vitro and in vivo antitumour effects and possible underlying mechanisms of action of dihydroartemisinin (DHA), the most effective compound, were further determined in ovarian cancer cells. ARS compounds exerted potent cytotoxicity to human ovarian carcinoma cells, with minimal effects on non-tumourigenic ovarian surface epithelial (OSE) cells. DHA inhibited ovarian cancer cell growth when administered alone or in combination with carboplatin, presumably through the death receptor- and, mitochondrion-mediated caspase-dependent apoptotic pathway. These effects were also observed in in vivo ovarian A2780 and OVCAR-3 xenograft tumour models. In conclusion, ARS derivatives, particularly DHA, exhibit significant anticancer activity against ovarian cancer cells in vitro and in vivo, with minimal toxicity to non-tumourigenic human OSE cells, indicating that they may be promising therapeutic agents for ovarian cancer, either used alone or in combination with conventional chemotherapy.

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DHA selectively decreases cell viability and inhibits the growth of human ovarian carcinoma cells, but not non-tumourigenic ovarian surface epithe-lial cells. (A) Chemical structures of the four artemisinin (ARS) compounds; (B) Viability of human ovarian carcinoma cells (ovarian carcinoma A2780 and OVCAR-3) and non-tumourigenic OSE cells (IOSE144) after 48 hrs exposure to the ARS compounds as determined by MTT assay; C, Cell growth inhibition after 0, 24, 48 and 72 hrs exposure of A2780 and OVCAR-3 cells to DHA. Values are representative of at least three independent experiments with similar results, and are presented as the percentage of cell inhibition where vehicle-treated cells were regarded as 100% viable/0% growth inhibition.
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fig01: DHA selectively decreases cell viability and inhibits the growth of human ovarian carcinoma cells, but not non-tumourigenic ovarian surface epithe-lial cells. (A) Chemical structures of the four artemisinin (ARS) compounds; (B) Viability of human ovarian carcinoma cells (ovarian carcinoma A2780 and OVCAR-3) and non-tumourigenic OSE cells (IOSE144) after 48 hrs exposure to the ARS compounds as determined by MTT assay; C, Cell growth inhibition after 0, 24, 48 and 72 hrs exposure of A2780 and OVCAR-3 cells to DHA. Values are representative of at least three independent experiments with similar results, and are presented as the percentage of cell inhibition where vehicle-treated cells were regarded as 100% viable/0% growth inhibition.

Mentions: Artemisinin (ARS), a sesquiterpene lactone anti-malarial drug, and its analogues, including dihydroartemisinin (DHA), artesunate (ART) and artemether (ARM) (Fig. 1), have been used in the clinic for many years [8–10], and have recently been suggested to have anticancer effects [9, 11–19]. The mechanisms of action for their antitumour activities are not fully understood, but may include selective cytotoxicity of cancer cells [9, 13], induction of apoptosis [20–23], modulation of gene expression [22, 24–28], causation of cell cycle arrest [23, 29–31] and inhibition of angiogenesis [17, 23, 28, 32–34].


Dihydroartemisinin induces apoptosis and sensitizes human ovarian cancer cells to carboplatin therapy.

Chen T, Li M, Zhang R, Wang H - J. Cell. Mol. Med. (2008)

DHA selectively decreases cell viability and inhibits the growth of human ovarian carcinoma cells, but not non-tumourigenic ovarian surface epithe-lial cells. (A) Chemical structures of the four artemisinin (ARS) compounds; (B) Viability of human ovarian carcinoma cells (ovarian carcinoma A2780 and OVCAR-3) and non-tumourigenic OSE cells (IOSE144) after 48 hrs exposure to the ARS compounds as determined by MTT assay; C, Cell growth inhibition after 0, 24, 48 and 72 hrs exposure of A2780 and OVCAR-3 cells to DHA. Values are representative of at least three independent experiments with similar results, and are presented as the percentage of cell inhibition where vehicle-treated cells were regarded as 100% viable/0% growth inhibition.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4496149&req=5

fig01: DHA selectively decreases cell viability and inhibits the growth of human ovarian carcinoma cells, but not non-tumourigenic ovarian surface epithe-lial cells. (A) Chemical structures of the four artemisinin (ARS) compounds; (B) Viability of human ovarian carcinoma cells (ovarian carcinoma A2780 and OVCAR-3) and non-tumourigenic OSE cells (IOSE144) after 48 hrs exposure to the ARS compounds as determined by MTT assay; C, Cell growth inhibition after 0, 24, 48 and 72 hrs exposure of A2780 and OVCAR-3 cells to DHA. Values are representative of at least three independent experiments with similar results, and are presented as the percentage of cell inhibition where vehicle-treated cells were regarded as 100% viable/0% growth inhibition.
Mentions: Artemisinin (ARS), a sesquiterpene lactone anti-malarial drug, and its analogues, including dihydroartemisinin (DHA), artesunate (ART) and artemether (ARM) (Fig. 1), have been used in the clinic for many years [8–10], and have recently been suggested to have anticancer effects [9, 11–19]. The mechanisms of action for their antitumour activities are not fully understood, but may include selective cytotoxicity of cancer cells [9, 13], induction of apoptosis [20–23], modulation of gene expression [22, 24–28], causation of cell cycle arrest [23, 29–31] and inhibition of angiogenesis [17, 23, 28, 32–34].

Bottom Line: The in vitro and in vivo antitumour effects and possible underlying mechanisms of action of dihydroartemisinin (DHA), the most effective compound, were further determined in ovarian cancer cells.These effects were also observed in in vivo ovarian A2780 and OVCAR-3 xenograft tumour models.In conclusion, ARS derivatives, particularly DHA, exhibit significant anticancer activity against ovarian cancer cells in vitro and in vivo, with minimal toxicity to non-tumourigenic human OSE cells, indicating that they may be promising therapeutic agents for ovarian cancer, either used alone or in combination with conventional chemotherapy.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, PR China.

ABSTRACT
The present study was designed to determine the effects of artemisinin (ARS) and its derivatives on human ovarian cancer cells, to evaluate their potential as novel chemotherapeutic agents used alone or in combination with a conventional cancer chemotherapeutic agent, and to investigate their underlying mechanisms of action. Human ovarian cancer cells (A2780 and OVCAR-3), and immortalized non-tumourigenic human ovarian surface epithelial cells (IOSE144), were exposed to four ARS compounds for cytotoxicity testing. The in vitro and in vivo antitumour effects and possible underlying mechanisms of action of dihydroartemisinin (DHA), the most effective compound, were further determined in ovarian cancer cells. ARS compounds exerted potent cytotoxicity to human ovarian carcinoma cells, with minimal effects on non-tumourigenic ovarian surface epithelial (OSE) cells. DHA inhibited ovarian cancer cell growth when administered alone or in combination with carboplatin, presumably through the death receptor- and, mitochondrion-mediated caspase-dependent apoptotic pathway. These effects were also observed in in vivo ovarian A2780 and OVCAR-3 xenograft tumour models. In conclusion, ARS derivatives, particularly DHA, exhibit significant anticancer activity against ovarian cancer cells in vitro and in vivo, with minimal toxicity to non-tumourigenic human OSE cells, indicating that they may be promising therapeutic agents for ovarian cancer, either used alone or in combination with conventional chemotherapy.

Show MeSH
Related in: MedlinePlus