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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 inhibits tumor growth in xenograft mice modelsSix-week-old NOD/SCID mice were subcutaneously injected in the right flank area with 2 × 107 cells of U266. When tumor volume reached to 50 mm3 after inoculation, mice (n = 6/group) were each given every 2–3 days intraperitionial (i.p.) injection of icaritin at 3-or 6 mg/kg in DMSO or bortezomib at 0.75 mg/kg in PBS, Control mice were given the solvent vehicle. A. Tumor volume was measured every other day with caliper and calculated according to the formula: V = 0.5 × a × b2. Mean ± SD, Statistical significance was determined by ANOVA, asterisks (***) represent significant (p < 0.001) differences relative to controls. B and C. Mice were sacrificed after 21 days of treatment, and the tumors were excised and weighed. The tumor weights represent the Mean ± SD. *p < 0.05; ***p < 0.001. D. the body weight of mice was measured on alternate days during the experiments. Results represent the Mean ± SD.
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Figure 5: Icaritin inhibits tumor growth in xenograft mice modelsSix-week-old NOD/SCID mice were subcutaneously injected in the right flank area with 2 × 107 cells of U266. When tumor volume reached to 50 mm3 after inoculation, mice (n = 6/group) were each given every 2–3 days intraperitionial (i.p.) injection of icaritin at 3-or 6 mg/kg in DMSO or bortezomib at 0.75 mg/kg in PBS, Control mice were given the solvent vehicle. A. Tumor volume was measured every other day with caliper and calculated according to the formula: V = 0.5 × a × b2. Mean ± SD, Statistical significance was determined by ANOVA, asterisks (***) represent significant (p < 0.001) differences relative to controls. B and C. Mice were sacrificed after 21 days of treatment, and the tumors were excised and weighed. The tumor weights represent the Mean ± SD. *p < 0.05; ***p < 0.001. D. the body weight of mice was measured on alternate days during the experiments. Results represent the Mean ± SD.

Mentions: We next assessed whether icaritin could inhibit tumor growth in vivo with using immunoincompetent mice. U266 cells were subcutaneously inoculated into NOD/SCID mice in the right flank area. After tumors volume grew to 50 mm3, the mice were administered icarritin (3 mg/kg or 6 mg/kg) or bortezomib (0.75 mg/kg) every 2–3 day with intraperitoneal injection (i.p). Tumor growth and mice body weight were monitored every other day for 21 days. As show in Figure 5A, 5B and 5C, icaritin resulted in potent inhibition of tumor growth. In icaritin-treated group (6 mg/kg), the effect of icaritin on growth-inhibition was stronger than bortezomib-treated groups (Figure 5B, 5C). Moreover, body weight loss was not observed in icaritin-treated groups. At the end of experiment (the 21st day), in icaritin-treated groups, the body weight was 17.2 g ± 1.17 g, which is comparable to the control group 17.02 g ± 1.21 g (Figure 5D).


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 inhibits tumor growth in xenograft mice modelsSix-week-old NOD/SCID mice were subcutaneously injected in the right flank area with 2 × 107 cells of U266. When tumor volume reached to 50 mm3 after inoculation, mice (n = 6/group) were each given every 2–3 days intraperitionial (i.p.) injection of icaritin at 3-or 6 mg/kg in DMSO or bortezomib at 0.75 mg/kg in PBS, Control mice were given the solvent vehicle. A. Tumor volume was measured every other day with caliper and calculated according to the formula: V = 0.5 × a × b2. Mean ± SD, Statistical significance was determined by ANOVA, asterisks (***) represent significant (p < 0.001) differences relative to controls. B and C. Mice were sacrificed after 21 days of treatment, and the tumors were excised and weighed. The tumor weights represent the Mean ± SD. *p < 0.05; ***p < 0.001. D. the body weight of mice was measured on alternate days during the experiments. Results represent the Mean ± SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Icaritin inhibits tumor growth in xenograft mice modelsSix-week-old NOD/SCID mice were subcutaneously injected in the right flank area with 2 × 107 cells of U266. When tumor volume reached to 50 mm3 after inoculation, mice (n = 6/group) were each given every 2–3 days intraperitionial (i.p.) injection of icaritin at 3-or 6 mg/kg in DMSO or bortezomib at 0.75 mg/kg in PBS, Control mice were given the solvent vehicle. A. Tumor volume was measured every other day with caliper and calculated according to the formula: V = 0.5 × a × b2. Mean ± SD, Statistical significance was determined by ANOVA, asterisks (***) represent significant (p < 0.001) differences relative to controls. B and C. Mice were sacrificed after 21 days of treatment, and the tumors were excised and weighed. The tumor weights represent the Mean ± SD. *p < 0.05; ***p < 0.001. D. the body weight of mice was measured on alternate days during the experiments. Results represent the Mean ± SD.
Mentions: We next assessed whether icaritin could inhibit tumor growth in vivo with using immunoincompetent mice. U266 cells were subcutaneously inoculated into NOD/SCID mice in the right flank area. After tumors volume grew to 50 mm3, the mice were administered icarritin (3 mg/kg or 6 mg/kg) or bortezomib (0.75 mg/kg) every 2–3 day with intraperitoneal injection (i.p). Tumor growth and mice body weight were monitored every other day for 21 days. As show in Figure 5A, 5B and 5C, icaritin resulted in potent inhibition of tumor growth. In icaritin-treated group (6 mg/kg), the effect of icaritin on growth-inhibition was stronger than bortezomib-treated groups (Figure 5B, 5C). Moreover, body weight loss was not observed in icaritin-treated groups. At the end of experiment (the 21st day), in icaritin-treated groups, the body weight was 17.2 g ± 1.17 g, which is comparable to the control group 17.02 g ± 1.21 g (Figure 5D).

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