Effects of 3-styrylchromones on Metabolic Profiles and Cell Death in Oral Squamous Cell Carcinoma Cells

Overview

Journal Toxicol Rep

Date 2017 Oct 1

PMID 28962471

Citations 17

Authors

Hiroshi Sakagami

Chiyako Shimada

Yumiko Kanda

Osamu Amano

Masahiro Sugimoto

Sana Ota

Tomoyoshi Soga

Masaru Tomita

Akira Sato

Sei-Ichi Tanuma

Koichi Takao

Yoshiaki Sugita

Affiliations

Soon will be listed here.

Abstract

4-1-benzopyran-4-ones (chromones) are important naturally-distributing compounds. As compared with flavones, isoflavones and 2-styrylchromones, there are only few papers of 3-styrylchromones that have been published. We have previously reported that among fifteen 3-styrylchromone derivatives, three new synthetic compounds that have OCH group at the C-6 position of chromone ring, ()-3-(4-hydroxystyryl)-6-methoxy-4-chromen-4-one (compound ), ()-6-methoxy-3-(4-methoxystyryl)-4-chromen-4-one (compound ), ()-6-methoxy-3-(3,4,5-trimethoxystyryl)-4-chromen-4-one (compound ) showed much higher cytotoxicities against four epithelial human oral squamous cell carcinoma (OSCC) lines than human normal oral mesenchymal cells. In order to further confirm the tumor specificities of these compounds, we compared their cytotoxicities against both human epithelial malignant and non-malignant cells, and then investigated their effects on fine cell structures and metabolic profiles and cell death in human OSCC cell line HSC-2. Cytotoxicities of compounds , , were assayed with MTT method. Fine cell structures were observed under transmission electron microscope. Cellular metabolites were extracted with methanol and subjected to CE-TOFMS analysis. Compounds , , showed much weaker cytotoxicity against human oral keratinocyte and primary human gingival epithelial cells, as compared with HSC-2, confirming their tumor-specificity, whereas doxorubicin and 5-FU were highly cytotoxic to these normal epithelial cells, giving unexpectedly lower tumor-specificity. The most cytotoxic compound , induced the mitochondrial vacuolization, autophagy suppression followed by apoptosis induction, and changes in the metabolites involved in amino acid and glycerophospholipid metabolisms. Chemical modification of lead compound may be a potential choice for designing new type of anticancer drugs.

Citing Articles

A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs.

Abe T, Sakagami H, Amano S, Uota S, Bandow K, Uesawa Y Medicines (Basel). 2023; 10(7).

PMID: 37505064 PMC: 10386476. DOI: 10.3390/medicines10070043.

Dichloroacetyl Amides of 3,5-Bis(benzylidene)-4-piperidones Displaying Greater Toxicity to Neoplasms than to Non-Malignant Cells.

Hossain M, Roayapalley P, Sakagami H, Satoh K, Bandow K, Das U Medicines (Basel). 2022; 9(6).

PMID: 35736248 PMC: 9228592. DOI: 10.3390/medicines9060035.

A Dual Anti-Inflammatory and Anti-Proliferative 3-Styrylchromone Derivative Synergistically Enhances the Anti-Cancer Effects of DNA-Damaging Agents on Colon Cancer Cells by Targeting HMGB1-RAGE-ERK1/2 Signaling.

Tanuma S, Oyama T, Okazawa M, Yamazaki H, Takao K, Sugita Y Int J Mol Sci. 2022; 23(7).

PMID: 35408786 PMC: 8998738. DOI: 10.3390/ijms23073426.

Styrylchromones: Biological Activities and Structure-Activity Relationship.

Lucas M, Freitas M, Silva A, Fernandes E, Ribeiro D Oxid Med Cell Longev. 2022; 2021:2804521.

PMID: 34987699 PMC: 8720608. DOI: 10.1155/2021/2804521.

Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts.

Roayapalley P, Dimmock J, Contreras L, Balderrama K, Aguilera R, Sakagami H Molecules. 2021; 26(23).

PMID: 34885719 PMC: 8659243. DOI: 10.3390/molecules26237132.

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