Molecular Mechanisms Underlying Yatein-Induced Cell-Cycle Arrest and Microtubule Destabilization in Human Lung Adenocarcinoma Cells.

Shang-Tse Ho,Jyh-Horng Wu,Yu-Tang Tung,Chi-Chen Lin

doi:10.3390/cancers11091384

Abstract

Yatein is an antitumor agent isolated from Calocedrus formosana Florin leaves extract. In our previous study, we found that yatein inhibited the growth of human lung adenocarcinoma A549 and CL1-5 cells by inducing intrinsic and extrinsic apoptotic pathways. To further uncover the effects and mechanisms of yatein-induced inhibition on A549 and CL1-5 cell growth, we evaluated yatein-mediated antitumor activity in vivo and the regulatory effects of yatein on cell-cycle progression and microtubule dynamics. Flow cytometry and western blotting revealed that yatein induces G2/M arrest in A549 and CL1-5 cells. Yatein also destabilized microtubules and interfered with microtubule dynamics in the two cell lines. Furthermore, we evaluated the antitumor activity of yatein in vivo using a xenograft mouse model and found that yatein treatment altered cyclin B/Cdc2 complex expression and significantly inhibited tumor growth. Taken together, our results suggested that yatein effectively inhibited the growth of A549 and CL1-5 cells possibly by disrupting cell-cycle progression and microtubule dynamics.

Highlights

Natural products have been used for treating disease for thousands of years
To address whether yatein induced DNA damage in cells, we examined the effects of yatein treatment on the ATM/ATR pathway
The present study demonstrated that yatein suppressed lung adenocarcinoma cancer cells growth by inducing cell-cycle arrest, mitotic catastrophe, and microtubule depolymerization

Summary

Introduction

Natural products have been used for treating disease for thousands of years. Natural products are being continuously developed for pharmaceutical applications, for anticancer, antibacterial, and antiviral applications [1]. Explorative and mechanistic studies on new bioactive compounds are still ongoing. Cells routinely come in contact with endogenous and exogenous stress stimuli, such as toxic chemicals, UV radiation, and reactive oxygen species. These stress stimuli damage chromosomes, affecting DNA replication and chromosome segregation [2]. Each phase of the cell cycle, including

Methods

Discussion

Conclusion