Honokiol suppresses metastasis of renal cell carcinoma by targeting KISS1/KISS1R signaling
- Shujie Cheng
- Victor Castillo
- Isaac Eliaz
- Daniel Sliva
Affiliations: Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN, USA, Amitabha Medical Clinic and Healing Center, Santa Rosa, CA, USA
- Published online on: April 2, 2015 https://doi.org/10.3892/ijo.2015.2950
Copyright: © Cheng
et al. This is an open access article distributed under the
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Commons Attribution License [CC BY_NC 3.0].
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Renal cell carcinoma (RCC) is a common urological cancer worldwide and is known to have a high risk of metastasis, which is considered responsible for more than 90% of cancer associated deaths. Honokiol is a small-molecule biphenol isolated from Magnolia spp. bark and has been shown to be a potential anticancer agent involved in multiple facets of signal transduction. In this study, we demonstrated that honokiol inhibited the invasion and colony formation of highly metastatic RCC cell line 786-0 in a dose-dependent manner. DNA-microarray data showed the significant upregulation of metastasis-suppressor gene KISS1 and its receptor, KISS1R. The upregulation was confirmed by qRT-PCR analysis. Overexpression of KISS1 and KISS1R was detected by western blotting at the translation level as well. Of note, the decreased invasive and colonized capacities were reversed by KISS1 knockdown. Taken together, the results first indicate that activation of KISS1/KISS1R signaling by honokiol suppresses multistep process of metastasis, including invasion and colony formation, in RCC cells 786-0. Honokiol may be considered as a natural agent against RCC metastasis.