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Icaritin suppresses multiple myeloma, by inhibiting IL-6/JAK2/STAT3.

Zhu S, Wang Z, Li Z, Peng H, Luo Y, Deng M, Li R, Dai C, Xu Y, Liu S, Zhang G - Oncotarget (2015)

Bottom Line: In contrast, icaritin had low or no cytotoxic effect on normal hematopoiesis.We also demonstrated that in MM xenograft mouse models, icaritin suppressed tumor growth and decreased serum IL-6 and IgE levels, but did not show adverse reactions such as body weight loss.The anti-MM activity of icaritin was mainly mediated by inhibiting IL-6/JAK2/STAT3 signaling.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology, Institute of Molecular Hematology, The Second Xiang-ya Hospital, Central South University, Changsha, Hunan, China.

ABSTRACT
Icaritin is an active prenylflavonoid derived from Epimedium genus, a traditional Chinese medicine. Icaritin has a wide range of pharmacological and biological activities, including cardiovascular function improvement, hormone regulation and antitumor activity. Here, we investigated the effect of icaritin on multiple myeloma (MM) in vitro and in vivo. Icaritin inhibited cell growth of MM cell line and primary MM cells. In contrast, icaritin had low or no cytotoxic effect on normal hematopoiesis. We also demonstrated that in MM xenograft mouse models, icaritin suppressed tumor growth and decreased serum IL-6 and IgE levels, but did not show adverse reactions such as body weight loss. The anti-MM activity of icaritin was mainly mediated by inhibiting IL-6/JAK2/STAT3 signaling. We suggest that icaritin can be further tested in clinical trials in MM.

No MeSH data available.


Related in: MedlinePlus

Icaritin induces U266 cells or CD138+ primary MM cells apoptosisA and B. U266 cells and CD138+ primary MM cells were treated with increasing concentrations of icaritin for 48 h, which was followed by analysis of apoptosis by staining with PI and Annexin-V FITC. Annexin-V positive cells were measured by flow cytometry. Columns represent the average percent of Annexin V positive cells from more than 3 independent experiments, which are shown as the mean ± SD. Asterisks (***) indicates statistically significant (p < 0.001) differences. Asterisks (**) or (*) represents statistically significant differences (p < 0.01) or p < 0.05, respectively. Representative images are shown in the left panel. C. Effects of icaritin on casepase 3, caspase 9, bak, bax, bcl-xl expression (western blot results). β-actin is used as loading control. D. Morphological features for apoptosis in untreated and icaritin-treated U266 were revealed by Wright-Giemsa staining under light microscope (Carl Zeiss Axio Scope A1) at 400× magnification.
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Figure 2: Icaritin induces U266 cells or CD138+ primary MM cells apoptosisA and B. U266 cells and CD138+ primary MM cells were treated with increasing concentrations of icaritin for 48 h, which was followed by analysis of apoptosis by staining with PI and Annexin-V FITC. Annexin-V positive cells were measured by flow cytometry. Columns represent the average percent of Annexin V positive cells from more than 3 independent experiments, which are shown as the mean ± SD. Asterisks (***) indicates statistically significant (p < 0.001) differences. Asterisks (**) or (*) represents statistically significant differences (p < 0.01) or p < 0.05, respectively. Representative images are shown in the left panel. C. Effects of icaritin on casepase 3, caspase 9, bak, bax, bcl-xl expression (western blot results). β-actin is used as loading control. D. Morphological features for apoptosis in untreated and icaritin-treated U266 were revealed by Wright-Giemsa staining under light microscope (Carl Zeiss Axio Scope A1) at 400× magnification.

Mentions: To confirm whether the anti-tumor activity of icaritin is associated with apoptosis, we assessed morphologic changes in icaritin-treated cells. U266 exposed to different concentrations of icaritin for 48 h displayed morphologic characteristics of apoptosis such as condensation of nuclear, membrane blebbing, as revealed by light microscope with Wright-Giemsa staining (Figure 2D). Externalized phosphatidylserine (PS), an indicator of early apoptosis, as revealed with the annexin V-FITC staining, was remarkably increased both in icaritin-treated U266 cells and CD138+ MM cells (Figure 2A, 2B). To evaluate the molecular events of apoptosis arising from icaritin treatment, western blot was performed for detecting the expression of caspase 3, caspase 9, Bax, Bak and Bcl-xL proteins. As shown in Figure 2C, icaritin significantly upregulated the expression of Bak and Bax and inhibited Bcl-xL expression with dose-dependent manner. Following increased icaritin concentration, caspase 3 and caspase 9 were cleaved and activated. These results suggest that icarritin induced MM cells apoptosis is involved in caspases pathway.


Icaritin suppresses multiple myeloma, by inhibiting IL-6/JAK2/STAT3.

Zhu S, Wang Z, Li Z, Peng H, Luo Y, Deng M, Li R, Dai C, Xu Y, Liu S, Zhang G - Oncotarget (2015)

Icaritin induces U266 cells or CD138+ primary MM cells apoptosisA and B. U266 cells and CD138+ primary MM cells were treated with increasing concentrations of icaritin for 48 h, which was followed by analysis of apoptosis by staining with PI and Annexin-V FITC. Annexin-V positive cells were measured by flow cytometry. Columns represent the average percent of Annexin V positive cells from more than 3 independent experiments, which are shown as the mean ± SD. Asterisks (***) indicates statistically significant (p < 0.001) differences. Asterisks (**) or (*) represents statistically significant differences (p < 0.01) or p < 0.05, respectively. Representative images are shown in the left panel. C. Effects of icaritin on casepase 3, caspase 9, bak, bax, bcl-xl expression (western blot results). β-actin is used as loading control. D. Morphological features for apoptosis in untreated and icaritin-treated U266 were revealed by Wright-Giemsa staining under light microscope (Carl Zeiss Axio Scope A1) at 400× magnification.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496367&req=5

Figure 2: Icaritin induces U266 cells or CD138+ primary MM cells apoptosisA and B. U266 cells and CD138+ primary MM cells were treated with increasing concentrations of icaritin for 48 h, which was followed by analysis of apoptosis by staining with PI and Annexin-V FITC. Annexin-V positive cells were measured by flow cytometry. Columns represent the average percent of Annexin V positive cells from more than 3 independent experiments, which are shown as the mean ± SD. Asterisks (***) indicates statistically significant (p < 0.001) differences. Asterisks (**) or (*) represents statistically significant differences (p < 0.01) or p < 0.05, respectively. Representative images are shown in the left panel. C. Effects of icaritin on casepase 3, caspase 9, bak, bax, bcl-xl expression (western blot results). β-actin is used as loading control. D. Morphological features for apoptosis in untreated and icaritin-treated U266 were revealed by Wright-Giemsa staining under light microscope (Carl Zeiss Axio Scope A1) at 400× magnification.
Mentions: To confirm whether the anti-tumor activity of icaritin is associated with apoptosis, we assessed morphologic changes in icaritin-treated cells. U266 exposed to different concentrations of icaritin for 48 h displayed morphologic characteristics of apoptosis such as condensation of nuclear, membrane blebbing, as revealed by light microscope with Wright-Giemsa staining (Figure 2D). Externalized phosphatidylserine (PS), an indicator of early apoptosis, as revealed with the annexin V-FITC staining, was remarkably increased both in icaritin-treated U266 cells and CD138+ MM cells (Figure 2A, 2B). To evaluate the molecular events of apoptosis arising from icaritin treatment, western blot was performed for detecting the expression of caspase 3, caspase 9, Bax, Bak and Bcl-xL proteins. As shown in Figure 2C, icaritin significantly upregulated the expression of Bak and Bax and inhibited Bcl-xL expression with dose-dependent manner. Following increased icaritin concentration, caspase 3 and caspase 9 were cleaved and activated. These results suggest that icarritin induced MM cells apoptosis is involved in caspases pathway.

Bottom Line: In contrast, icaritin had low or no cytotoxic effect on normal hematopoiesis.We also demonstrated that in MM xenograft mouse models, icaritin suppressed tumor growth and decreased serum IL-6 and IgE levels, but did not show adverse reactions such as body weight loss.The anti-MM activity of icaritin was mainly mediated by inhibiting IL-6/JAK2/STAT3 signaling.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology, Institute of Molecular Hematology, The Second Xiang-ya Hospital, Central South University, Changsha, Hunan, China.

ABSTRACT
Icaritin is an active prenylflavonoid derived from Epimedium genus, a traditional Chinese medicine. Icaritin has a wide range of pharmacological and biological activities, including cardiovascular function improvement, hormone regulation and antitumor activity. Here, we investigated the effect of icaritin on multiple myeloma (MM) in vitro and in vivo. Icaritin inhibited cell growth of MM cell line and primary MM cells. In contrast, icaritin had low or no cytotoxic effect on normal hematopoiesis. We also demonstrated that in MM xenograft mouse models, icaritin suppressed tumor growth and decreased serum IL-6 and IgE levels, but did not show adverse reactions such as body weight loss. The anti-MM activity of icaritin was mainly mediated by inhibiting IL-6/JAK2/STAT3 signaling. We suggest that icaritin can be further tested in clinical trials in MM.

No MeSH data available.


Related in: MedlinePlus