Cheng Shujie, Castillo Victor, Welty Matt, Eliaz Isaac, Sliva Daniel
Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN, USA.
Amitabha Medical Clinic and Healing Center, Santa Rosa, CA, USA.
Int J Oncol. 2016 Oct;49(4):1525-1530. doi: 10.3892/ijo.2016.3663. Epub 2016 Aug 19.
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.
厚朴酚是一种从厚朴树皮中分离出的生物活性化合物，已显示出通过诱导细胞凋亡具有有前景的抗癌作用。然而，关于其抗转移活性的信息相对较少。肾细胞癌（RCC）是成人肾脏最常见的恶性肿瘤，以高转移风险著称。临床上，转移性RCC病例的治疗方法有限，开发新治疗方法的努力仍在进行中。我们当前研究的结果首次揭示，厚朴酚可抑制不同人肾癌细胞的增殖而不影响细胞活力。此外，厚朴酚抑制高转移性肾癌细胞786-0的迁移，并刺激小GTP酶RhoA的活性。此外，在用厚朴酚处理的786-0细胞中鉴定出磷酸化肌球蛋白轻链（MLC）和肌动蛋白应激纤维的过度形成。有趣的是，药理学上的Rho相关蛋白激酶（ROCK）抑制剂Y-27632减弱了厚朴酚诱导的肌动蛋白应激纤维收缩，并消除了厚朴酚介导的细胞迁移抑制。这些重要发现共同表明，厚朴酚通过激活RhoA/ROCK/MLC信号传导抑制高转移性肾癌细胞的迁移，作为一种新的治疗方法，在肾癌细胞转移治疗中值得关注。
