Isokotomolide A from Cinnamomum kotoense Induce Melanoma Autophagy and Apoptosis In Vivo and In Vitro.

Jian Li,Zixuan Xu,Jyun Yin Huang,Lin Wang,Chung-Yi Chen,Hui-Min David Wang,Wenyi Kang,Miao-Hsia Lin

doi:10.1155/2020/3425147

Abstract

Melanoma is an aggressive cancer with high lethality. In order to find new anticancer agents, isokotomolide A (Iso A) and secokotomolide A (Sec A) isolated from Cinnamomum kotoense were identified to be potential bioactive agents against human melanoma but without strong antioxidative properties. Cell proliferation assay displayed Iso A and Sec A treated in the normal human skin cells showed high viabilities. It also verified that two of them possess strong antimelanoma effect in concentration-dependent manners, especially on B16F10, A2058, MeWo, and A375 cells. Wound healing assay presented their excellent antimigratory effects. Through 3-N,3-N,6-N,6-N-Tetramethylacridine-3,6-diamine (acridine orange, AO) staining and Western blot, the autophagy induced by treatment was confirmed, including autophagy-related proteins (Atgs). By using annexin V–FITC/PI double-stain, the apoptosis was confirmed, and both components also triggered the cell cycle arrest and DNA damage. We demonstrated the correlations between the mitogen-activated protein kinase (MAPK) pathway and antimelanoma, such as caspase cascade activations. To further evaluate in vivo experiments, the inhibition of tumor cell growth was verified through the histopathological staining in a xenograft model. In this study, it was confirmed that Iso A and Sec A can encourage melanoma cell death via early autophagy and late apoptosis processes.

Highlights

Skin cancer is one of the most aggressive malignant tumors, which especially occurs in people with light skin
We investigated the effects of isokotomolide A (Iso A) and secokotomolide A (Sec A) on the suppressions in cellular proliferation, cell cycle arrest, cell migration, and the activations of autophagy and apoptosis pathways, and in vivo examinations
Since melanomas occur on the skin and most of them are caused by UV exposure, the impacts of oxidative stresses on melanoma have attracted researchers’ attentions

Summary

Introduction

Skin cancer is one of the most aggressive malignant tumors, which especially occurs in people with light skin. There are three skin cancers: squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma. SCC is a kind of abnormal cell cancer with uncontrolled growth arising from the squamous cells. It can occur in all areas of the body and are the most common in the areas exposed to sunlight. SCC possesses the ability of metastasis and can harm other areas of the body. BCC and SCC are defined as nonmelanoma skin cancer (NMSC) [3]. Malignant melanoma is highly aggressive which develops from the pigment-containing cells known as melanocytes.

Objectives

Methods

Results

Conclusion