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

Abstract

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.

Honokiol inhibits in vitro and in vivo growth of oral squamous cell carcinoma through induction of apoptosis, cell cycle arrest and autophagy

“…Honokiol has been described to regulate multiple signalling pathways, molecular and cellular targets including nuclear factor‐κB (NF‐κB), STAT3, epidermal growth factor receptor (EGFR), c‐Met, c‐FLIP, bone morphogenetic protein 7 (BMP7), p53, RhoA, cell survival signalling and cell cycle mediators . To identify the mechanisms involved in honokiol‐mediated growth inhibition of OSCC cells, three survival signalling including p38, Erk and JNK pathways and four autophagy‐related signalling pathways including AMPK, Akt/mTOR, BNIP3 and Beclin‐1 were examined.…”

“…GAPDH was used as an internal control. signalling and cell cycle mediators [11,[49][50][51][52]. To identify the mechanisms involved in honokiol-mediated growth inhibition of OSCC cells, three survival signalling including p38, Erk and JNK pathways and four autophagy-related signalling pathways including AMPK, Akt/ mTOR, BNIP3 and Beclin-1 were examined.…”

Honokiol: A Review of Its Anticancer Potential and Mechanisms

“…Therefore, one of the important steps in cancer management is to control tumour cell metastasis, especially for early-stage cancer patients [153]. Various studies have reported that honokiol has the capability to suppress tumour metastasis in different types of cancer including breast cancer [40,148,154], non-small cell lung cancer [44,155] ovarian carcinoma cells [28], lung cancer [50], U251 human glioma, as well as U-87MG and T98G human glioblastoma cell [63,65,94], oral squamous cell carcinoma (OSCC) [26], bladder cancer cell [143], pancreatic cancer [58], renal cell carcinoma [156,157], and gastric cancer cells [113]. For instance, the percentage of invading urinary bladder cancer (UBC) cells was significantly reduced by 67% and 92% upon 2.4 µg/mL and 4.8 µg/mL of honokiol treatment, respectively [143].…”

Honokiol induces apoptosis of lung squamous cell carcinoma by targeting FGF2‐FGFR1 autocrine loop

“…Our study indicated that honokiol administration could downregulate BCL2 expression, promote the caspase‐3 signaling pathway, and accelerate cell apoptosis. Cell migration is an important process in tumor metastasis and progression . Several studies have reported that honokiol can inhibit the migration of various kinds of malignancies under different mechanisms .…”