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Huaier Extract Induces Autophagic Cell Death by Inhibiting the mTOR/S6K Pathway in Breast Cancer Cells.

Wang X, Qi W, Li Y, Zhang N, Dong L, Sun M, Cun J, Zhang Y, Lv S, Yang Q - PLoS ONE (2015)

Bottom Line: Huaier extract is attracting increased attention due to its biological activities, including antitumor, anti-parasite and immunomodulatory effects.Inhibition of autophagy attenuated Huaier-induced cell death.After implanting MDA-MB-231 cells subcutaneously into the right flank of BALB/c nu/nu mice, Huaier extract induced autophagy and effectively inhibited xenograft tumor growth.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, P.R. China.

ABSTRACT
Huaier extract is attracting increased attention due to its biological activities, including antitumor, anti-parasite and immunomodulatory effects. Here, we investigated the role of autophagy in Huaier-induced cytotoxicity in MDA-MB-231, MDA-MB-468 and MCF7 breast cancer cells. Huaier treatment inhibited cell viability in all three cell lines and induced various large membranous vacuoles in the cytoplasm. In addition, electron microscopy, MDC staining, accumulated expression of autophagy markers and flow cytometry revealed that Huaier extract triggered autophagy. Inhibition of autophagy attenuated Huaier-induced cell death. Furthermore, Huaier extract inhibited the mammalian target of the rapamycin (mTOR)/S6K pathway in breast cancer cells. After implanting MDA-MB-231 cells subcutaneously into the right flank of BALB/c nu/nu mice, Huaier extract induced autophagy and effectively inhibited xenograft tumor growth. This study is the first to show that Huaier-induced cytotoxicity is partially mediated through autophagic cell death in breast cancer cells through suppression of the mTOR/S6K pathway.

No MeSH data available.


Related in: MedlinePlus

Huaier extract inhibited the growth of breast cancer cells in vivo by inducing autophagy.(A) MDA-MB-231 cells were subcutaneously implanted into the right flank of BALB/c nu/nu mice as described in the materials and methods section. Mice with xenograft tumors were photographed after treatment with PBS (control), Huaier alone or in combination with chloroquine (15 mg/kg once daily) on day 32. (B) The mean volumes of xenograft tumors were measured at 4-day intervals with calipers. Growth curves of xenograft tumors are shown. (C) Representative micrographs of immunohistochemical staining using anti-LC3B antibody. Bars, 30 μm. (D) Western blot analysis of protein expression in tumors taken from mice.
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pone.0131771.g006: Huaier extract inhibited the growth of breast cancer cells in vivo by inducing autophagy.(A) MDA-MB-231 cells were subcutaneously implanted into the right flank of BALB/c nu/nu mice as described in the materials and methods section. Mice with xenograft tumors were photographed after treatment with PBS (control), Huaier alone or in combination with chloroquine (15 mg/kg once daily) on day 32. (B) The mean volumes of xenograft tumors were measured at 4-day intervals with calipers. Growth curves of xenograft tumors are shown. (C) Representative micrographs of immunohistochemical staining using anti-LC3B antibody. Bars, 30 μm. (D) Western blot analysis of protein expression in tumors taken from mice.

Mentions: In order to determine whether Huaier extract could inhibit tumor growth in vivo, MDA-MB-231 breast cancer cells were incubated subcutaneously into the right flank of BALB/c nu/nu mice. As shown in Fig 6, Huaier extract treatment inhibited xenograft tumor growth in comparison to the control group. On day 32, the tumor size of the Huaier-treated group significantly diminished from 487.5 ± 30.41 mm3 in the control group to 42.5 ± 3.54 mm3 in the Huaier-treated group (see Fig 6). When the mice were co-treated with chloroquine and Huaier extract, the inhibitory effect of Huaier extract on tumor growth was partially rescued.


Huaier Extract Induces Autophagic Cell Death by Inhibiting the mTOR/S6K Pathway in Breast Cancer Cells.

Wang X, Qi W, Li Y, Zhang N, Dong L, Sun M, Cun J, Zhang Y, Lv S, Yang Q - PLoS ONE (2015)

Huaier extract inhibited the growth of breast cancer cells in vivo by inducing autophagy.(A) MDA-MB-231 cells were subcutaneously implanted into the right flank of BALB/c nu/nu mice as described in the materials and methods section. Mice with xenograft tumors were photographed after treatment with PBS (control), Huaier alone or in combination with chloroquine (15 mg/kg once daily) on day 32. (B) The mean volumes of xenograft tumors were measured at 4-day intervals with calipers. Growth curves of xenograft tumors are shown. (C) Representative micrographs of immunohistochemical staining using anti-LC3B antibody. Bars, 30 μm. (D) Western blot analysis of protein expression in tumors taken from mice.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4489895&req=5

pone.0131771.g006: Huaier extract inhibited the growth of breast cancer cells in vivo by inducing autophagy.(A) MDA-MB-231 cells were subcutaneously implanted into the right flank of BALB/c nu/nu mice as described in the materials and methods section. Mice with xenograft tumors were photographed after treatment with PBS (control), Huaier alone or in combination with chloroquine (15 mg/kg once daily) on day 32. (B) The mean volumes of xenograft tumors were measured at 4-day intervals with calipers. Growth curves of xenograft tumors are shown. (C) Representative micrographs of immunohistochemical staining using anti-LC3B antibody. Bars, 30 μm. (D) Western blot analysis of protein expression in tumors taken from mice.
Mentions: In order to determine whether Huaier extract could inhibit tumor growth in vivo, MDA-MB-231 breast cancer cells were incubated subcutaneously into the right flank of BALB/c nu/nu mice. As shown in Fig 6, Huaier extract treatment inhibited xenograft tumor growth in comparison to the control group. On day 32, the tumor size of the Huaier-treated group significantly diminished from 487.5 ± 30.41 mm3 in the control group to 42.5 ± 3.54 mm3 in the Huaier-treated group (see Fig 6). When the mice were co-treated with chloroquine and Huaier extract, the inhibitory effect of Huaier extract on tumor growth was partially rescued.

Bottom Line: Huaier extract is attracting increased attention due to its biological activities, including antitumor, anti-parasite and immunomodulatory effects.Inhibition of autophagy attenuated Huaier-induced cell death.After implanting MDA-MB-231 cells subcutaneously into the right flank of BALB/c nu/nu mice, Huaier extract induced autophagy and effectively inhibited xenograft tumor growth.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, P.R. China.

ABSTRACT
Huaier extract is attracting increased attention due to its biological activities, including antitumor, anti-parasite and immunomodulatory effects. Here, we investigated the role of autophagy in Huaier-induced cytotoxicity in MDA-MB-231, MDA-MB-468 and MCF7 breast cancer cells. Huaier treatment inhibited cell viability in all three cell lines and induced various large membranous vacuoles in the cytoplasm. In addition, electron microscopy, MDC staining, accumulated expression of autophagy markers and flow cytometry revealed that Huaier extract triggered autophagy. Inhibition of autophagy attenuated Huaier-induced cell death. Furthermore, Huaier extract inhibited the mammalian target of the rapamycin (mTOR)/S6K pathway in breast cancer cells. After implanting MDA-MB-231 cells subcutaneously into the right flank of BALB/c nu/nu mice, Huaier extract induced autophagy and effectively inhibited xenograft tumor growth. This study is the first to show that Huaier-induced cytotoxicity is partially mediated through autophagic cell death in breast cancer cells through suppression of the mTOR/S6K pathway.

No MeSH data available.


Related in: MedlinePlus