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Honokiol inhibits migration of renal cell carcinoma through activation of RhoA/ROCK/MLC signaling pathway

Shujie Cheng1, Victor Castillo1, Matt Welty1

  • 1Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN, USA.

International Journal of Oncology
|September 17, 2016
PubMed

Insights

Honokiol, a compound from Magnolia bark, inhibits renal cell carcinoma (RCC) migration by activating RhoA/ROCK/MLC signaling. This suggests honokiol as a potential new treatment for metastatic RCC.

Area of Science:

  • Oncology
  • Pharmacology
  • Cell Biology

Background:

  • Honokiol, derived from Magnolia bark, demonstrates anticancer properties via apoptosis induction.
  • Limited data exists on honokiol's anti-metastatic effects, particularly for renal cell carcinoma (RCC), a highly metastatic malignancy.
  • Current treatments for metastatic RCC are limited, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To investigate the anti-metastatic potential of honokiol in human renal cell carcinoma (RCC) models.
  • To elucidate the underlying molecular mechanisms of honokiol's effect on RCC cell migration.

Main Methods:

  • Assessed honokiol's effect on RCC cell proliferation and viability.
  • Evaluated honokiol's impact on the migration of highly metastatic RCC 786-0 cells.
  • Analyzed the involvement of RhoA/ROCK/MLC signaling pathway components, including RhoA activity, phosphorylated myosin light chain (MLC), and actin stress fibers.
  • Utilized the Rho-associated protein kinase (ROCK) inhibitor Y-27632 to confirm the role of the RhoA/ROCK pathway.

Main Results:

  • Honokiol suppressed proliferation of various human RCC cell lines without affecting cell viability.
  • Honokiol inhibited migration of highly metastatic RCC 786-0 cells and stimulated RhoA activity.
  • Treatment with honokiol led to increased phosphorylated myosin light chain (MLC) and actin stress fiber formation.
  • The ROCK inhibitor Y-27632 reversed honokiol-induced actin stress fiber contraction and abrogated the inhibition of cell migration.

Conclusions:

  • Honokiol effectively suppresses the migration of highly metastatic renal cell carcinoma cells.
  • The anti-migratory effect of honokiol is mediated through the activation of the RhoA/ROCK/MLC signaling pathway.
  • Honokiol represents a promising novel therapeutic agent for treating renal cell carcinoma metastasis.

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