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Tetrandrine induces autophagy and differentiation by activating ROS and Notch1 signaling in leukemia cells.

Liu T, Men Q, Wu G, Yu C, Huang Z, Liu X, Li W - Oncotarget (2015)

Bottom Line: Tetrandrine is a traditional Chinese medicinal herb extract with antitumor effects.The in vivo results indicated that low concentrations of tetrandrine inhibited leukemia cells proliferation and induced autophagy and then facilitated their differentiation, by activating ROS and Notch1 signaling.We suggest that tetrandrine is a potential agent for the treatment of APL by inducing differentiation of leukemia cells.

View Article: PubMed Central - PubMed

Affiliation: College of Life Sciences, Wuhan University, Wuhan, P. R. China.

ABSTRACT
All-trans retinoic acid (ATRA) is a differentiating agent for the treatment of acute promyelocytic leukemia (APL). However, the therapeutic efficacy of ATRA has limitations. Tetrandrine is a traditional Chinese medicinal herb extract with antitumor effects. In this study, we investigated the effects of tetrandrine on human PML-RARα-positive acute promyelocytic leukemia cells. Tetrandrine inhibited tumors in vivo. It induced autophagy and differentiation by triggering ROS generation and activating Notch1 signaling. Tetrandrine induced autophagy and differentiation in M5 type patient primary leukemia cells. The in vivo results indicated that low concentrations of tetrandrine inhibited leukemia cells proliferation and induced autophagy and then facilitated their differentiation, by activating ROS and Notch1 signaling. We suggest that tetrandrine is a potential agent for the treatment of APL by inducing differentiation of leukemia cells.

No MeSH data available.


Related in: MedlinePlus

Tetrandrine induced autophagy and differentiation in M5 type patient primary leukemia cellsM5 leukemia is one subtype of acute myeloid leukemia (AML). (A) Western blot analysis of LC3 protein levels. M5 type patient cells were treated with 2 μM tetrandrine (Tet) for 24 hours. (B) Acridine orange staining assay analysis of autophagy in M5 type patient cells. Cells were treated with 2 μM tetrandrine (Tet) for 24 hours. Error bars represent the mean ±SD. **p <0.01. (C) Flow cytometry analysis of CD11b and CD14 expression. M5 type patient cells were treated with 2 μM tetrandrine (Tet) for 4 days.
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Figure 2: Tetrandrine induced autophagy and differentiation in M5 type patient primary leukemia cellsM5 leukemia is one subtype of acute myeloid leukemia (AML). (A) Western blot analysis of LC3 protein levels. M5 type patient cells were treated with 2 μM tetrandrine (Tet) for 24 hours. (B) Acridine orange staining assay analysis of autophagy in M5 type patient cells. Cells were treated with 2 μM tetrandrine (Tet) for 24 hours. Error bars represent the mean ±SD. **p <0.01. (C) Flow cytometry analysis of CD11b and CD14 expression. M5 type patient cells were treated with 2 μM tetrandrine (Tet) for 4 days.

Mentions: M5 leukemia, or acute monocytic leukemia, is one of the most common subtypes of AML. To assess the effects of tetrandrine on human primary leukemia cells, we treated primary leukemia cells obtained from M5 type patients who had not previously received chemotherapy. The results showed that tetrandrine treatment dramatically promoted LC3 protein expression as well as an increased accumulation of acidic autophagolysosome vacuoles (Fig. 2A and B). In addition, tetrandrine treatment also facilitated the expression of CD11b and CD14 on the surface of M5 type patient cells (Fig. 2C). These results revealed that tetrandrine exhibited considerable effects on the differentiation of M5 type patient primary leukemia cells.


Tetrandrine induces autophagy and differentiation by activating ROS and Notch1 signaling in leukemia cells.

Liu T, Men Q, Wu G, Yu C, Huang Z, Liu X, Li W - Oncotarget (2015)

Tetrandrine induced autophagy and differentiation in M5 type patient primary leukemia cellsM5 leukemia is one subtype of acute myeloid leukemia (AML). (A) Western blot analysis of LC3 protein levels. M5 type patient cells were treated with 2 μM tetrandrine (Tet) for 24 hours. (B) Acridine orange staining assay analysis of autophagy in M5 type patient cells. Cells were treated with 2 μM tetrandrine (Tet) for 24 hours. Error bars represent the mean ±SD. **p <0.01. (C) Flow cytometry analysis of CD11b and CD14 expression. M5 type patient cells were treated with 2 μM tetrandrine (Tet) for 4 days.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480730&req=5

Figure 2: Tetrandrine induced autophagy and differentiation in M5 type patient primary leukemia cellsM5 leukemia is one subtype of acute myeloid leukemia (AML). (A) Western blot analysis of LC3 protein levels. M5 type patient cells were treated with 2 μM tetrandrine (Tet) for 24 hours. (B) Acridine orange staining assay analysis of autophagy in M5 type patient cells. Cells were treated with 2 μM tetrandrine (Tet) for 24 hours. Error bars represent the mean ±SD. **p <0.01. (C) Flow cytometry analysis of CD11b and CD14 expression. M5 type patient cells were treated with 2 μM tetrandrine (Tet) for 4 days.
Mentions: M5 leukemia, or acute monocytic leukemia, is one of the most common subtypes of AML. To assess the effects of tetrandrine on human primary leukemia cells, we treated primary leukemia cells obtained from M5 type patients who had not previously received chemotherapy. The results showed that tetrandrine treatment dramatically promoted LC3 protein expression as well as an increased accumulation of acidic autophagolysosome vacuoles (Fig. 2A and B). In addition, tetrandrine treatment also facilitated the expression of CD11b and CD14 on the surface of M5 type patient cells (Fig. 2C). These results revealed that tetrandrine exhibited considerable effects on the differentiation of M5 type patient primary leukemia cells.

Bottom Line: Tetrandrine is a traditional Chinese medicinal herb extract with antitumor effects.The in vivo results indicated that low concentrations of tetrandrine inhibited leukemia cells proliferation and induced autophagy and then facilitated their differentiation, by activating ROS and Notch1 signaling.We suggest that tetrandrine is a potential agent for the treatment of APL by inducing differentiation of leukemia cells.

View Article: PubMed Central - PubMed

Affiliation: College of Life Sciences, Wuhan University, Wuhan, P. R. China.

ABSTRACT
All-trans retinoic acid (ATRA) is a differentiating agent for the treatment of acute promyelocytic leukemia (APL). However, the therapeutic efficacy of ATRA has limitations. Tetrandrine is a traditional Chinese medicinal herb extract with antitumor effects. In this study, we investigated the effects of tetrandrine on human PML-RARα-positive acute promyelocytic leukemia cells. Tetrandrine inhibited tumors in vivo. It induced autophagy and differentiation by triggering ROS generation and activating Notch1 signaling. Tetrandrine induced autophagy and differentiation in M5 type patient primary leukemia cells. The in vivo results indicated that low concentrations of tetrandrine inhibited leukemia cells proliferation and induced autophagy and then facilitated their differentiation, by activating ROS and Notch1 signaling. We suggest that tetrandrine is a potential agent for the treatment of APL by inducing differentiation of leukemia cells.

No MeSH data available.


Related in: MedlinePlus