Abstract. Honokiol, a biologically active compound isolated from Magnolia bark, has been shown to possess promising anticancer effect through induction of apoptosis. However, there is a relative lack of information regarding its anti-metastatic activity. Renal cell carcinoma (RCC) is the most common malignancy of the adult kidney and is known for high risk of metastasis. Clinically, therapeutic methods for metastatic RCC cases are limited and efforts to exploit new treatments are still ongoing. The results of our current investigation first revealed that honokiol suppressed the proliferation of different human RCCs without affecting cell viability. In addition, honokiol inhibited migration of highly metastatic RCC 786-0 cells and stimulated the activity of small GTPase, RhoA. Furthermore, phosphorylated myosin light chain (MLC) and excessive formation of actin stress fibers were identified in 786-0 cells treated with honokiol. Interestingly, the pharmacological Rho-associated protein kinase (ROCK) inhibitor Y-27632 attenuated contraction of actin stress fibers induced by honokiol and abrogated honokiol-mediated inhibition of cell migration. Together these important findings suggest that honokiol suppresses the migration of highly metastatic RCC through activation of RhoA/ROCK/MLC signaling and warrants attention in the treatment of RCC metastasis as a novel therapeutic approach.

BackgroundTamoxifen (TAM) has been widely used for the treatment of estrogen receptor (ER)-positive breast cancer and its combination with other therapies is being actively investigated as a way to increase efficacy and decrease side effects. Here, we evaluate the therapeutic potential of co-treatment with TAM and BreastDefend (BD), a dietary supplement formula, in ER-positive human breast cancer.MethodsCell proliferation and apoptosis were determined in ER-positive human breast cancer cells MCF-7 by MTT assay, quantitation of cytoplasmic histone-associated DNA fragments and expression of cleaved PARP, respectively. The molecular mechanism was identified using RNA microarray analysis and western blotting. Tumor tissues from xenograft mouse model were analyzed by immunohistochemistry.ResultsOur data clearly demonstrate that a combination of 4-hydroxytamoxifen (4-OHT) with BD lead to profound inhibition of cell proliferation and induction of apoptosis in MCF-7 cells. This effect is consistent with the regulation of apoptotic and TAM resistant genes at the transcription and translation levels. Importantly, TAM and BD co-treatment significantly enhanced apoptosis, suppressed tumor growth and reduced tumor weight in a xenograft model of human ER-positive breast cancer.ConclusionBD sensitized ER-positive human breast cancer cells to 4-OHT/TAM treatment in vitro and in vivo. BreastDefend can be used in an adjuvant therapy to increase the therapeutic effect of tamoxifen in patients with ER-positive breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-017-1621-7) contains supplementary material, which is available to authorized users.

Renal cell carcinoma (RCC) is a common urological cancer worldwide and is known to the high risk of recurrence and metastasis. Approximately 70% of patients with RCC will develop recurrence after surgical resection, and 25%-30% of patients will eventually develop progression to distant metastasis. Honokiol is a small-molecule polyphenol isolated from the genus Magnolia, which has been shown to be a potential anticancer agent in multiple facets of signal transduction. Here we demonstrate that honokiol inhibits proliferation of RCC cells 786-0 and A498 without affecting cell viability. Moreover, honokiol also significantly inhibited migration of 786-0 cells in a dose-dependent manner. DNA microarray analysis showed that honokiol regulated expression of many genes related to human tumor metastasis in 786-0 cells. Real time PCR analysis confirmed that the expression of metastasis suppressor KISS1 and its receptor, KISS1R, were upregulated in 786-0 cells after treatment with honokiol. In addition, the shape changes and excessive formation of actin stress fibers were identified in 786-0 cells treated with honokiol. This phenomenon disappeared when treated cells with the pharmacological Rho-kinase inhibitor Y-27632 and honokiol. This inhibition can also be identified in 786-0 cells treated with Y-27632 only. Our present results demonstrated that honokiol could inhibit the growth and migration of RCC, which is likely to be regulated by the Rho and Rho-Associated Kinase (ROCK) pathway. In conclusion, honokiol is a biologically active natural compound which can be considered for the alternative treatment of RCC. The investigation of detailed mechanisms and molecular targets are in progress. Citation Format: Shujie Cheng, Matt Welty, Isaac Eliaz, Victor Castillo, Daniel Sliva. Honokiol inhibits growth and migration of renal cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3203. doi:10.1158/1538-7445.AM2014-3203