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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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Western blot analysis of protein expression levels indicating the effects of DHA on A2780 and OVCAR-3 ovarian cancer cell lines after 24 hrs exposure to specific dosesof DHA.
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fig03: Western blot analysis of protein expression levels indicating the effects of DHA on A2780 and OVCAR-3 ovarian cancer cell lines after 24 hrs exposure to specific dosesof DHA.

Mentions: To confirm the effects on apoptosis, we evaluated the expression of apoptosis-related proteins, including PARP, Bax, Bcl-2 and Bid (see Fig. 3). We observed a dose-dependent increase in cleaved-PARP and Bax, while there was a dose-dependent decrease in Bcl-2 and Bid. Moreover, we investigated the expression of pro-caspases-3, 9 and 8, and observed a dose-dependent cleavage, indicative of caspase activation. We also observed a dose-dependent up-regulation of Fas and its downstream adaptor protein, FADD, which can activate caspase-8, the main enzyme responsible for truncation of Bid. These data indicate that the activation of caspases plays a major role in the apoptosis induced by DHA, and that this apparently occurs via activation of the death receptor pathway.


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)

Western blot analysis of protein expression levels indicating the effects of DHA on A2780 and OVCAR-3 ovarian cancer cell lines after 24 hrs exposure to specific dosesof DHA.
© Copyright Policy
Related In: Results  -  Collection

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

fig03: Western blot analysis of protein expression levels indicating the effects of DHA on A2780 and OVCAR-3 ovarian cancer cell lines after 24 hrs exposure to specific dosesof DHA.
Mentions: To confirm the effects on apoptosis, we evaluated the expression of apoptosis-related proteins, including PARP, Bax, Bcl-2 and Bid (see Fig. 3). We observed a dose-dependent increase in cleaved-PARP and Bax, while there was a dose-dependent decrease in Bcl-2 and Bid. Moreover, we investigated the expression of pro-caspases-3, 9 and 8, and observed a dose-dependent cleavage, indicative of caspase activation. We also observed a dose-dependent up-regulation of Fas and its downstream adaptor protein, FADD, which can activate caspase-8, the main enzyme responsible for truncation of Bid. These data indicate that the activation of caspases plays a major role in the apoptosis induced by DHA, and that this apparently occurs via activation of the death receptor pathway.

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