Honokiol inhibits bladder tumor growth by suppressing EZH2/miR-143 axis

Urinary bladder cancer (UBC) is one of the most common urogenital malignant tumors, with an estimated 74,690 new cases and 15,580 deaths occurring in USA during 2014. Although localized bladder cancers can be surgically resected, the recurrence and progression rates are extremely high. Moreover, the therapeutic response from the patients with advanced bladder cancer with radio or chemotherapy is very limited. Therefore, UBC is one of the most expensive malignancies, with the annual cost at 4 billion US$ for UBC in the USA per year. Recent studies revealed that a small population of cancer stem cells (CSCs), which is enriched after therapy, may account for chemotherapy failure. These CSCs have the ability to generate all types of differentiated cells to repopulate tumors and eventually lead to metastasis; they are thus regarded as the sustaining force of a tumor.

In this study the effects of honokiol were determined by the mechanism of repression of oncoprotein EZH2 and induction of tumor suppressor miR-143, on the UBC cell proliferation, survival, cancer stemness maintenance and cell migration in vitro and in vivo. The honokiol treatment on T24 tumor xenografts confirmed its anticancer effects in vivo, including suppression of tumor growth and tumor stemness, accompanied by the dysregulation of EZH2 and miR- 143 expressions.

The novel mechanism how EZH2 directly regulates miR-143 in UBC cells has also been uncovered in the study. It was revealed that EZH2 could directly bind to the transcriptional regulatory region of miR-143 and repress its expression.

Overall this suggests a promising therapeutic option to develop drugs targeting EZH2/miR-143 axis, such as honokiol, for bladder cancer treatment.

You can find the study here.

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