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Anti-cancer effect of Cordyceps militaris in human colorectal carcinoma RKO cells via cell cycle arrest and mitochondrial apoptosis.

Lee HH, Lee S, Lee K, Shin YS, Kang H, Cho H - Daru (2015)

Bottom Line: Different types of Cordyceps extract were reported to have various pharmacological activities including an anti-cancer effect.Lastly, the effect of Cordyceps militaris on cell cycle as well as apoptosis was measured using flow cytometry.The anti-tumor effect of Cordyceps militaris was associated with an induction of cell cycle arrest and mitochondrial-mediated apoptosis.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Duksung Women's University, Seoul, 132-714, Republic of Korea. oeo3oeo@gmail.com.

ABSTRACT

Background: Cordyceps militaris has been used as a traditional medicine in Asian countries for a long time. Different types of Cordyceps extract were reported to have various pharmacological activities including an anti-cancer effect. We investigated the inhibitory effect of Cordyceps militaris ethanol extract on a human colorectal cancer-derived cell line, RKO.

Methods: RKO cells were treated with various concentrations of nucleosides-enriched ethanol extract of Cordyceps militaris for 48 h and cytotoxicity was measured using a CCK-8 assay. Then, xenograft Balb/c nude mice were injected with RKO cells and subsequently orally administered with ethanol extract of Cordyceps militaris every day for 3 weeks to examine the inhibitory effect on tumor growth. Lastly, the effect of Cordyceps militaris on cell cycle as well as apoptosis was measured using flow cytometry. Also, the expression of p53, caspase 9, cleaved caspase-3, cleaved PARP, Bim, Bax, Bak, and Bad were detected using western blot assay.

Results: RKO cells were highly susceptible to the ethanol extract of Cordyceps militaris (CME) and the growth of RKO cells-derived tumor was significantly delayed by the treatment of Cordyceps militaris. Cordyceps militaris induced cell cycle arrest in G2/M phase (untreated; 20.5 %, CME 100 μg/ml; 61.67 %, CME 300 μg/ml; 66.33 %) and increased early apoptosis (untreated; 1.01 %, CME 100 μg/ml; 8.48 %, CME 300 μg/ml; 18.07 %). The expression of p53, cleaved caspase 9, cleaved caspase-3, cleaved PARP, Bim, Bak, and Bad were upregulated by the treatment of Cordyceps militaris.

Conclusion: Ethanol extract of Cordyceps militaris was highly cytotoxic to human colorectal carcinoma RKO cells and inhibited the growth of tumor in xenograft model. The anti-tumor effect of Cordyceps militaris was associated with an induction of cell cycle arrest and mitochondrial-mediated apoptosis.

No MeSH data available.


Related in: MedlinePlus

Induction of mitochondrial-mediated apoptosis by Cordyceps militaris in a p53-dependent manner. Cells were treated with or without ethanol extract of Cordyceps militaris (CME) (0, 100, and 300 μg/ml) for 48 h and then western blot analysis for various apoptotic related molecules were performed. β-actin served as the loading control. a Expression of p53 and Bcl-2 family proteins. b Expression of caspases 9, 7, and 3, and PARP proteins. c The relative intensity of each band compared to the loading control
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Fig5: Induction of mitochondrial-mediated apoptosis by Cordyceps militaris in a p53-dependent manner. Cells were treated with or without ethanol extract of Cordyceps militaris (CME) (0, 100, and 300 μg/ml) for 48 h and then western blot analysis for various apoptotic related molecules were performed. β-actin served as the loading control. a Expression of p53 and Bcl-2 family proteins. b Expression of caspases 9, 7, and 3, and PARP proteins. c The relative intensity of each band compared to the loading control

Mentions: In addition, the release of cytochrome c is known to activate caspase-9 and caspase-3. Activation of caspase 3 triggers the cleavage of PARP (89 and 24 kDa), which functions to prevent DNA damage [25]. As shown in Fig. 5b, the extract of Cordyceps militaris increased the cleaved forms of caspases 9 and 3, which are final effector molecules in mitochondrial apoptosis.Fig. 5


Anti-cancer effect of Cordyceps militaris in human colorectal carcinoma RKO cells via cell cycle arrest and mitochondrial apoptosis.

Lee HH, Lee S, Lee K, Shin YS, Kang H, Cho H - Daru (2015)

Induction of mitochondrial-mediated apoptosis by Cordyceps militaris in a p53-dependent manner. Cells were treated with or without ethanol extract of Cordyceps militaris (CME) (0, 100, and 300 μg/ml) for 48 h and then western blot analysis for various apoptotic related molecules were performed. β-actin served as the loading control. a Expression of p53 and Bcl-2 family proteins. b Expression of caspases 9, 7, and 3, and PARP proteins. c The relative intensity of each band compared to the loading control
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4491205&req=5

Fig5: Induction of mitochondrial-mediated apoptosis by Cordyceps militaris in a p53-dependent manner. Cells were treated with or without ethanol extract of Cordyceps militaris (CME) (0, 100, and 300 μg/ml) for 48 h and then western blot analysis for various apoptotic related molecules were performed. β-actin served as the loading control. a Expression of p53 and Bcl-2 family proteins. b Expression of caspases 9, 7, and 3, and PARP proteins. c The relative intensity of each band compared to the loading control
Mentions: In addition, the release of cytochrome c is known to activate caspase-9 and caspase-3. Activation of caspase 3 triggers the cleavage of PARP (89 and 24 kDa), which functions to prevent DNA damage [25]. As shown in Fig. 5b, the extract of Cordyceps militaris increased the cleaved forms of caspases 9 and 3, which are final effector molecules in mitochondrial apoptosis.Fig. 5

Bottom Line: Different types of Cordyceps extract were reported to have various pharmacological activities including an anti-cancer effect.Lastly, the effect of Cordyceps militaris on cell cycle as well as apoptosis was measured using flow cytometry.The anti-tumor effect of Cordyceps militaris was associated with an induction of cell cycle arrest and mitochondrial-mediated apoptosis.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Duksung Women's University, Seoul, 132-714, Republic of Korea. oeo3oeo@gmail.com.

ABSTRACT

Background: Cordyceps militaris has been used as a traditional medicine in Asian countries for a long time. Different types of Cordyceps extract were reported to have various pharmacological activities including an anti-cancer effect. We investigated the inhibitory effect of Cordyceps militaris ethanol extract on a human colorectal cancer-derived cell line, RKO.

Methods: RKO cells were treated with various concentrations of nucleosides-enriched ethanol extract of Cordyceps militaris for 48 h and cytotoxicity was measured using a CCK-8 assay. Then, xenograft Balb/c nude mice were injected with RKO cells and subsequently orally administered with ethanol extract of Cordyceps militaris every day for 3 weeks to examine the inhibitory effect on tumor growth. Lastly, the effect of Cordyceps militaris on cell cycle as well as apoptosis was measured using flow cytometry. Also, the expression of p53, caspase 9, cleaved caspase-3, cleaved PARP, Bim, Bax, Bak, and Bad were detected using western blot assay.

Results: RKO cells were highly susceptible to the ethanol extract of Cordyceps militaris (CME) and the growth of RKO cells-derived tumor was significantly delayed by the treatment of Cordyceps militaris. Cordyceps militaris induced cell cycle arrest in G2/M phase (untreated; 20.5 %, CME 100 μg/ml; 61.67 %, CME 300 μg/ml; 66.33 %) and increased early apoptosis (untreated; 1.01 %, CME 100 μg/ml; 8.48 %, CME 300 μg/ml; 18.07 %). The expression of p53, cleaved caspase 9, cleaved caspase-3, cleaved PARP, Bim, Bak, and Bad were upregulated by the treatment of Cordyceps militaris.

Conclusion: Ethanol extract of Cordyceps militaris was highly cytotoxic to human colorectal carcinoma RKO cells and inhibited the growth of tumor in xenograft model. The anti-tumor effect of Cordyceps militaris was associated with an induction of cell cycle arrest and mitochondrial-mediated apoptosis.

No MeSH data available.


Related in: MedlinePlus