Cucurbitacin B Induces Hypermethylation of Oncogenes in Breast Cancer Cells

Kanthanadon Dittharot; Sumana Dakeng; Parichat Suebsakwong; Apichart Suksamrarn; Pimpicha Patmasiriwat; Moltira Promkan

doi:10.1055/a-0791-1591

Planta Medica, Table of Contents

Planta Med 2019; 85(05): 370-378
DOI: 10.1055/a-0791-1591

Biological and Pharmacological Activity

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

Cucurbitacin B Induces Hypermethylation of Oncogenes in Breast Cancer Cells

Kanthanadon Dittharot

¹Office of Research Academic and Innovation, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

,

Sumana Dakeng

²Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand

,

Parichat Suebsakwong

³Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok, Thailand

,

Apichart Suksamrarn

³Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok, Thailand

,

Pimpicha Patmasiriwat

²Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand

,

Moltira Promkan

²Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand

› Author Affiliations

Abstract

Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations. Recent studies revealed that abnormal gene expression induced by epigenetic changes including aberrant promoter methylation plays a critical role in human breast carcinogenesis. Cucurbitacin B has antiproliferative activity against various human breast cancer cells, but the molecular mechanism is not completely understood. In this study, we explore the influence of cucurbitacin B from Trichosanthes cucumerina on the methylation status at the promoter of oncogenes c-Myc, cyclin D1, and survivin in breast cancer cell lines. Growth inhibitory effect of cucurbitacin B on breast cancer cells was assessed by MTT assay and colony formation assay. Methylation status of genomic DNA was determined by methylation-specific PCR. Gene and protein expression levels of all genes studied were analyzed by real-time RT-PCR and western blot. The results indicated that cucurbitacin B could inhibit cell growth in breast cancer cells. The oncogene promoters are usually hypomethylated in cancer cells. Upon cucurbitacin B treatment, upregulation of DNMT1 and obvious heavy methylation in the promoters of c-Myc, cyclin D1, and survivin, which consequently downregulated the expression of all these oncogenes, were observed. Hence, cucurbitacin B proved to be a potential cancer therapeutic agent, in part by inducing hypermethylation and silences the oncogenic activation.

Key words

cucurbitacin B - Trichosanthes cucumerina - Curcubitaceae - hypermethylation - breast cancer - anticancer

Full Text

References

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