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JA, a new type of polyunsaturated fatty acid isolated from Juglans mandshurica Maxim, limits the survival and induces apoptosis of heptocarcinoma cells

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Juglans mandshurica Maxim (Juglandaceae) is a famous folk medicine for cancer treatment and some natural compounds isolated from it have been studied extensively. Previously we isolated a type of ω-9 polyunsaturated fatty acid (JA) from the bark of J. mandshurica, however little is known about its activity and the underlying mechanisms. In this study, we studied anti-tumor activity of JA on several human cancer cell lines. Results showed that JA is cytotoxic to HepG2, MDA-MB-231, SGC-7901, A549 and Huh7 cells at a concentration exerting minimal toxic effects on L02 cells. The selective toxicity of JA was better than other classical anti-cancer drugs. Further investigation indicated that JA could induce cell apoptosis, characterized by chromatin condensation, DNA fragmentation and activation of the apoptosis-associated proteins such as Caspase-3 and PARP-1. Moreover, we investigated the cellular apoptosis pathway involved in the apoptosis process in HepG2 cells. We found that proteins involved in mitochondrion (cleaved-Caspase-9, Apaf-1, HtrA2/Omi, Bax, and Mitochondrial Bax) and endocytoplasmic reticulum (XBP-1s, GRP78, cleaved-Caspase-7 and cleaved-Caspase-12) apoptotic pathways were up-regulated when cells were treated by JA. In addition, a morphological change in the mitochondrion was detected. Furthermore, we found that JA could inhibit DNA synthesis and induce G2/M cell cycle arrest. The expression of G2-to-M transition related proteins, such as CyclinB1 and phosphorylated-CDK1, were reduced. In contrast, the G2-to-M inhibitor p21 was increased in JA-treated cells. Overall, our results suggest that JA can induce mitochondrion- and endocytoplasmic reticulum-mediated apoptosis, and G2/M phase arrest in HepG2 cells, making it a promising therapeutic agent against hepatoma.

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Acknowledgments

We thank Chunlei Yu, Yanxiang Guo and Yao Yao for helpful guidance in experiment methods, Guannan Wang and Xiuli Wang for electron microscopy technology. This work was supported by grants from the National Natural Science Foundation of China (Nos. 31170324 and 31070318), the Fundamental Research Funds for the Central Universities (No. 11QNJJ021), and the Research Foundation of Jilin Provincial Science and Technology Development (No. 20140203008YY).

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Authors and Affiliations

  1. National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, 130024, China

    Xiu-Li Gao, Hua Lin, Yong-Li Bao & Lu-Guo Sun

  2. Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun, 130024, China

    Wei Zhao, Ya-Qin Hou, Zhen-Bo Song, Shang-Yi Tian & Yu-Xin Li

  3. Department of Hand Surgery, China-Japan Union Hospital, Jilin University, Changchun, 130024, China

    Biao Liu

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  1. Xiu-Li Gao
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Gao, XL., Lin, H., Zhao, W. et al. JA, a new type of polyunsaturated fatty acid isolated from Juglans mandshurica Maxim, limits the survival and induces apoptosis of heptocarcinoma cells. Apoptosis 21, 340–350 (2016). https://doi.org/10.1007/s10495-015-1202-5

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