Magnolol Inhibits the Growth of Non-Small Cell Lung Cancer via Inhibiting Microtubule Polymerization

Abstract

Background: The tubulin/microtubule system, which is an integral component of the cytoskeleton, plays an essential role in mitosis. Targeting mitotic progression by disturbing microtubule dynamics is a rational strategy for cancer treatment. Methods: Microtubule polymerization assay was performed to examine the effect of Magnolol (a novel natural phenolic compound isolated from Magnolia obovata) on cellular microtubule polymerization in human non-small cell lung cancer (NSCLC) cells. Cell cycle analysis, mitotic index assay, cell proliferation assay, colony formation assay, western blotting analysis of cell cycle regulators, Annexin V-FITC/PI staining, and live/dead viability staining were carried out to investigate the Magnolol’s inhibitory effect on proliferation and viability of NSCLS cells in vitro. Xenograft model of human A549 NSCLC tumor was used to determine the Magnolol’s efficacy in vivo. Results: Magnolol treatment effectively inhibited cell proliferation and colony formation of NSCLC cells. Further study proved that Magnolol induced the mitotic phase arrest and inhibited G2/M progression in a dose-dependent manner, which were mechanistically associated with expression alteration of a series of cell cycle regulators. Furthermore, Magnolol treatment disrupted the cellular microtubule organization via inhibiting the polymerization of microtubule. We also found treatment with NSCLC cells with Magnolol resulted in apoptosis activation through a p53-independent pathway, and autophgy induction via down-regulation of the Akt/mTOR pathway. Finally, Magnolol treatment significantly suppressed the NSCLC tumor growth in mouse xenograft model in vivo. Conclusion: These findings identify Magnolol as a promising candidate with anti-microtubule polymerization activity for NSCLC treatment.

Magnolol: A Neolignan from the Magnolia Family for the Prevention and Treatment of Cancer

“…Numerous preclinical studies have established that MAG exerts its effect on different types of human cancers such as those of lung, prostate, breast, gall bladder, colon, skin and hepatocellular carcinoma [50,51,52,53,54,55,56,57]. The plausible molecular mechanisms liable for the anti-cancer potential of MAG are reduced cell proliferation or cell cytotoxicity, induction of apoptosis, accumulation of reactive oxygen species (ROS), induction of autophagy and activation/inactivation of various cellular signaling pathways [46].…”

Suppression of Non-Small Cell Lung Cancer Growth and Metastasis by a Novel Small Molecular Activator of RECK

“…Lung cancer remains the leading cause of cancer-related mortality worldwide although the large number of clinical trials aimed at improving patients’ survival [16-18]. More than 1.5 million new cases of lung cancer are diagnosed every year, approximately 80% of which are NSCLC [19-21].…”

SKLB060 Reversibly Binds to Colchicine Site of Tubulin and Possesses Efficacy in Multidrug-Resistant Cell Lines

“…8B), which leads to an opening in the binding pocket for MPC-6827. Compared with the crystal structure of the tubulin-colchicine complex, MPC-6827 exhibited a similar binding mode to that of colchicine-located at the intrasubunit interface within the αβ tubulin heterodimer-which was in complete contrast to a previous docking study [30]. The quinazoline ring and the methoxy benzene group of MPC-6827 superimposed on the colchicine A and C rings, respectively, while the aminomethyl linker overlapped the B ring of colchicine (Fig.…”

“…An important function of microtubules is to form spindles and separate sister chromosomes into two daughter cells during cell division to help complete cell division [3,[29][30][31]. Microtubule inhibitors can inhibit this process by destroying the microtubules.…”