Aspernolide A Inhibits the Proliferation of Human Laryngeal Carcinoma Cells through the Mitochondrial Apoptotic and STAT3 Signaling Pathways.

Chang Liu,Ji Hao,Xinzhou Yang,Hong Liu,Huiqi Huang,Rui Qin,Yanzhang Wen,Yibing Lv

doi:10.3390/molecules24061074

Chang Liu, Ji Hao + Show 6 more

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https://doi.org/10.3390/molecules24061074

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Abstract

Aspernolide A, a butyrolactone secondary metabolite, was purified from the endophytic fungus Cladosporium cladosporioides derived from roots of Camptotheca acuminata Decne. In this study, the antitumor activity and mechanisms of aspernolide A on human laryngeal cancer Hep-2 and TU212 cells were studied by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, morphological observation and Western blotting. The results showed that aspernolide A significantly inhibited the proliferation of Hep-2 and TU212 cells in dose- and time-dependent manners. Morphological changes of apoptotic cells could be observed under an inverted microscope, such as irregular margins, decreased adherence ability and chromatin condensation. The expressions of Bax, Caspase-9, Caspase-3 and PARP (poly ADP-ribose polymerase) increased with the increase of dosage while Bcl-2 decreased, suggesting that the apoptotic mechanism might be related to the mitochondrial apoptotic pathway. Moreover, the expression of the phosphorylation of STAT3 decreased with the increase of dosage, suggesting that the apoptotic mechanism might be related to the STAT3 signaling pathway. All these conclusions indicated that aspernolide A has the potential anti-laryngocarcinoma effects.

Highlights

Laryngeal cancer is one of the most common malignant tumors of the head and neck [1]
ResultsIn the current research, we evaluated the cytotoxic activity of aspernolide A and preliminarily elucidated the antitumor mechanism of aspernolide A on Hep-2 and TU212 cell lines
We investigated the anti-proliferation of aspernolide A in Hep-2 and TU212 cells using MTT

Summary

Introduction

Laryngeal cancer is one of the most common malignant tumors of the head and neck [1]. The incidence of laryngeal squamous cell carcinoma ranks third among the tumors of the head and neck [2]. The European Cancer Observatory data for the European Union indicate that laryngeal squamous cell carcinoma (LSCC) is the 13th most common neoplasm in men [3]. The treatment of laryngeal cancer has undergone tremendous changes in the past few years. Therapy is determined by age, performance status, stage of disease and the tumour location [4]. Total laryngotomy is considered to be the most effective method for the treatment of laryngeal cancer, but costs a large amount, which brings some adverse sequelae to patients, such as hypothyroidism [5].

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