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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

Anti-cancer effect of Cordyceps militaris in a xenograft mouse bearing RKO cell–derived human colorectal cancer. Mice were injected with human colorectal carcinoma RKO cells (1 × 106 cells per mouse) subcutaneously into the back next to the right hind leg. Mice were sorted into 2 groups (n = 10/group) and orally administered ethanol extract of Cordyceps militaris (CME) (100 mg/kg) or drinking water. 14 days later, tumors were identified and measured every two days until the experimental endpoint. a Study design for animal experiment. b Photograph of xenograft mice bearing RKO cell-derived human colorectal cancer in right hind leg. The pictures of untreated and treated groups were taken at 13 days since the tumor volume was measured. c Inhibitory effect of Cordyceps militaris (CME) on RKO cell-derived tumor growth. Compared between drinking water group and CME group *P < 0.05. d Correlation of survival rate of xenograft mice bearing human colorectal cancer
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Fig2: Anti-cancer effect of Cordyceps militaris in a xenograft mouse bearing RKO cell–derived human colorectal cancer. Mice were injected with human colorectal carcinoma RKO cells (1 × 106 cells per mouse) subcutaneously into the back next to the right hind leg. Mice were sorted into 2 groups (n = 10/group) and orally administered ethanol extract of Cordyceps militaris (CME) (100 mg/kg) or drinking water. 14 days later, tumors were identified and measured every two days until the experimental endpoint. a Study design for animal experiment. b Photograph of xenograft mice bearing RKO cell-derived human colorectal cancer in right hind leg. The pictures of untreated and treated groups were taken at 13 days since the tumor volume was measured. c Inhibitory effect of Cordyceps militaris (CME) on RKO cell-derived tumor growth. Compared between drinking water group and CME group *P < 0.05. d Correlation of survival rate of xenograft mice bearing human colorectal cancer

Mentions: To evaluate the anti-cancer effect of ethanol extract of Cordyceps militaris in vivo, mice were injected subcutaneously with human colorectal cancer RKO cells (1 × 106 cells per mouse) and then ethanol extract of Cordyceps militaris (100 mg/kg) or drinking water was orally administrated every day for 3 weeks. Tumor growth was detected from all 20 mice and tumor volume was measured every two days until it reached 2000 mm3. Figure 2a displays the overall study design for animal experiment. Figure 2b shows representative photographs of xenograft mice bearing RKO cell-derived human colorectal cancer. The pictures of the extract fed and water fed groups were taken at 13 days since the tumor volume was measured. The size of tumors from the extract fed mice was smaller than that from water fed mice. In Fig. 2c, we confirmed that continuous feeding of ethanol extract of Cordyceps militaris (100 mg/kg) significantly inhibited the growth of RKO cell-derived tumors. We further determined whether inhibition of tumor growth directly correlates with survival rate in the xenograft animals. As expected, we observed a reduced mortality in mice administered 100 mg/kg of ethanol extract of Cordyceps militaris in Fig. 2d.Fig. 2


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)

Anti-cancer effect of Cordyceps militaris in a xenograft mouse bearing RKO cell–derived human colorectal cancer. Mice were injected with human colorectal carcinoma RKO cells (1 × 106 cells per mouse) subcutaneously into the back next to the right hind leg. Mice were sorted into 2 groups (n = 10/group) and orally administered ethanol extract of Cordyceps militaris (CME) (100 mg/kg) or drinking water. 14 days later, tumors were identified and measured every two days until the experimental endpoint. a Study design for animal experiment. b Photograph of xenograft mice bearing RKO cell-derived human colorectal cancer in right hind leg. The pictures of untreated and treated groups were taken at 13 days since the tumor volume was measured. c Inhibitory effect of Cordyceps militaris (CME) on RKO cell-derived tumor growth. Compared between drinking water group and CME group *P < 0.05. d Correlation of survival rate of xenograft mice bearing human colorectal cancer
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: Anti-cancer effect of Cordyceps militaris in a xenograft mouse bearing RKO cell–derived human colorectal cancer. Mice were injected with human colorectal carcinoma RKO cells (1 × 106 cells per mouse) subcutaneously into the back next to the right hind leg. Mice were sorted into 2 groups (n = 10/group) and orally administered ethanol extract of Cordyceps militaris (CME) (100 mg/kg) or drinking water. 14 days later, tumors were identified and measured every two days until the experimental endpoint. a Study design for animal experiment. b Photograph of xenograft mice bearing RKO cell-derived human colorectal cancer in right hind leg. The pictures of untreated and treated groups were taken at 13 days since the tumor volume was measured. c Inhibitory effect of Cordyceps militaris (CME) on RKO cell-derived tumor growth. Compared between drinking water group and CME group *P < 0.05. d Correlation of survival rate of xenograft mice bearing human colorectal cancer
Mentions: To evaluate the anti-cancer effect of ethanol extract of Cordyceps militaris in vivo, mice were injected subcutaneously with human colorectal cancer RKO cells (1 × 106 cells per mouse) and then ethanol extract of Cordyceps militaris (100 mg/kg) or drinking water was orally administrated every day for 3 weeks. Tumor growth was detected from all 20 mice and tumor volume was measured every two days until it reached 2000 mm3. Figure 2a displays the overall study design for animal experiment. Figure 2b shows representative photographs of xenograft mice bearing RKO cell-derived human colorectal cancer. The pictures of the extract fed and water fed groups were taken at 13 days since the tumor volume was measured. The size of tumors from the extract fed mice was smaller than that from water fed mice. In Fig. 2c, we confirmed that continuous feeding of ethanol extract of Cordyceps militaris (100 mg/kg) significantly inhibited the growth of RKO cell-derived tumors. We further determined whether inhibition of tumor growth directly correlates with survival rate in the xenograft animals. As expected, we observed a reduced mortality in mice administered 100 mg/kg of ethanol extract of Cordyceps militaris in Fig. 2d.Fig. 2

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