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Anti-tumor effect of emodin on gynecological cancer cells

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Abstract

Purpose

Although an anti-tumor effect of emodin has been reported before, its effect on human gynecological cancer cells has so far not been studied. Here, we assessed the effect of emodin on cervical cancer-derived (Hela), choriocarcinoma-derived (JAR) and ovarian cancer-derived (HO-8910) cells, and investigated the possible underlying molecular and cellular mechanisms.

Methods and results

The respective cells were treated with 0, 5, 10 or 15 μM emodin for 72 h. Subsequently, MTT and Transwell in vitro migration assays revealed that emodin significantly decreased the viability and invasive capacity of the gynecological cancer-derived cells tested. We found that emodin induced apoptosis and significantly decreased mitochondrial membrane potential and ATP release in these cells. We also found that emodin may exert its apoptotic effects via regulating the activity of caspase-9 and the expression of cleaved-caspase-3. Moreover, we found that emodin induced a cell cycle arrest at the G0/G1 phase, possibly through down-regulating the key cell cycle regulators Cyclin D and Cyclin E. Interestingly, emodin also led to autophagic cell death, as revealed by increased MAP LC3 expression, a marker of the autophagosome, and decreased expression of the autophagy regulators Beclin-1 and Atg12-Atg5. Finally, we found that the protein levels of both VEGF and VEGFR-2 were significantly decreased in emodin-treated cells, suggesting an anti-angiogenic effect of emodin on gynecological cancer-derived cells.

Conclusions

Our results suggest that emodin exhibits an anti-tumor effect on gynecological cancer-derived cells, possibly through multiple mechanisms including the induction of apoptosis and autophagy, the arrest of the cell cycle, and the inhibition of angiogenesis. Our findings may provide a basis for the design of potential emodin-based strategies for the treatment of gynecological tumors.

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Acknowledgement

This study was supported by funds from the Education Department of Heilongjiang Province (No. 12541274), the Postdoctoral Fund of Heilongjiang Province (No. LBH-Z13150), the Outstanding Youth Science Foundation of Heilongjiang Province (JC201108) and the National Natural Science Foundation (No. 81372786).

Conflict of interests

The authors declare that there is no conflict of interest.

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    Authors and Affiliations

    1. Department of Gynaecology, Harbin Medical University Cancer Hospital, 150 Hapin Road, Harbin, 150081, China

      Yaoxian Wang, Jing Gao, Yunyan Zhang & Ge Lou

    2. Cardiopulmonary Function Room, Harbin Medical University Cancer Hospital, Harbin, China

      Hui Yu

    3. Department of Gynaecology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China

      Jin Zhang

    4. Department of General Surgery, The Provincial Hospital of Heilongjiang, Harbin, China

      Xin Ge

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    1. Yaoxian Wang
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    Correspondence to Ge Lou.

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    Yaoxian Wang and Hui Yu contributed equally to this work.

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    Wang, Y., Yu, H., Zhang, J. et al. Anti-tumor effect of emodin on gynecological cancer cells. Cell Oncol. 38, 353–363 (2015). https://doi.org/10.1007/s13402-015-0234-8

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