Metabolic reprogramming and AMPKα1 pathway activation by caulerpin in colorectal cancer cells

  • Authors:
    • Hua Yu
    • Huiqin Zhang
    • Mingjun Dong
    • Zhou Wu
    • Zhonglei Shen
    • Yangyang Xie
    • Zhenfang Kong
    • Xiaoyu Dai
    • Binbin Xu
  • View Affiliations

  • Published online on: December 6, 2016     https://doi.org/10.3892/ijo.2016.3794
  • Pages: 161-172
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Abstract

Caulerpin, a secondary metabolite from the marine invasive green algae Caulerpa cylindracea is known to induce mitochondrial dysfunctions. In this study, the anticancer property of caulerpin was assessed in a panel of colorectal cancer cell lines. We demonstrated that caulerpin inhibited oxidative phosphorylation (OXPHOS) and facilitated an early intervention of the mitochondrial function, via inhibiting mitochondrial complex I, accompanied by the dissipation of mitochondrial membrane potential and a surge of reactive oxygen species (ROS) generation. Moreover, in response to the increment in AMP/ATP ratio, the energy sensor AMP-activated protein kinase (AMPK) was activated by caulerpin treatment in a calcium/calmodulin-dependent protein kinase 2 (CaMKK2)‑dependent manner. Distinguished effect on glycolysis was observed at different time-points after caulerpin treatment. Glycolysis was enhanced after a short time treatment with caulerpin, associated with upregulation of glucose transporter 1 (GLUT1), hexokinase II (HKII) and 6-phosphofructo-2-kinase (PFKFB3) protein expressions. However, long-term activation of AMPK by caulerpin damaged the glycolysis and glucose metabolism in colorectal cells, finally causing cell death. The persistent effect of caulerpin was mediated by AMPKα1, rather than AMPKα2, to abolish cell viability through hindering mTORC1-4E-BP1 axis. Moreover, caulerpin synergized with the glycolytic inhibitor 3BP in inhibiting cellular proliferation both in vitro and in vivo. Our findings on the previously uncharacterized anticancer effects of caulerpin may provide potential therapeutic approaches targeting the colorectal carcinoma metabolism.
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January-2017
Volume 50 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Yu H, Zhang H, Dong M, Wu Z, Shen Z, Xie Y, Kong Z, Dai X and Xu B: Metabolic reprogramming and AMPKα1 pathway activation by caulerpin in colorectal cancer cells. Int J Oncol 50: 161-172, 2017.
APA
Yu, H., Zhang, H., Dong, M., Wu, Z., Shen, Z., Xie, Y. ... Xu, B. (2017). Metabolic reprogramming and AMPKα1 pathway activation by caulerpin in colorectal cancer cells. International Journal of Oncology, 50, 161-172. https://doi.org/10.3892/ijo.2016.3794
MLA
Yu, H., Zhang, H., Dong, M., Wu, Z., Shen, Z., Xie, Y., Kong, Z., Dai, X., Xu, B."Metabolic reprogramming and AMPKα1 pathway activation by caulerpin in colorectal cancer cells". International Journal of Oncology 50.1 (2017): 161-172.
Chicago
Yu, H., Zhang, H., Dong, M., Wu, Z., Shen, Z., Xie, Y., Kong, Z., Dai, X., Xu, B."Metabolic reprogramming and AMPKα1 pathway activation by caulerpin in colorectal cancer cells". International Journal of Oncology 50, no. 1 (2017): 161-172. https://doi.org/10.3892/ijo.2016.3794