Publication: Trans-(−)-kusunokinin: A potential anticancer lignan compound against her2 in breast cancer cell lines?
Issued Date
2021-08-01
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ISSN
14203049
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2-s2.0-85111629861
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Mahidol University
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SCOPUS
Bibliographic Citation
Molecules. Vol.26, No.15 (2021)
Suggested Citation
Thidarath Rattanaburee, Tanotnon Tanawattanasuntorn, Tienthong Thongpanchang, Varomyalin Tipmanee, Potchanapond Graidist Trans-(−)-kusunokinin: A potential anticancer lignan compound against her2 in breast cancer cell lines?. Molecules. Vol.26, No.15 (2021). doi:10.3390/molecules26154537 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/76088
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Title
Trans-(−)-kusunokinin: A potential anticancer lignan compound against her2 in breast cancer cell lines?
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Abstract
Trans-(−)-kusunokinin, an anticancer compound, binds CSF1R with low affinity in breast cancer cells. Therefore, finding an additional possible target of trans-(−)-kusunokinin remains of importance for further development. Here, a computational study was completed followed by in-direct proof of specific target proteins using small interfering RNA (siRNA). Ten proteins in breast cancer were selected for molecular docking and molecular dynamics simulation. A preferred active form in racemic trans-(±)-kusunokinin was trans-(−)-kusunokinin, which had stronger binding energy on HER2 trans-(+)-kusunokinin; however, it was weaker than the designed HER inhibitors (03Q and neratinib). Predictively, trans-(−)-kusunokinin bound HER2 similarly to a reversible HER2 inhibitor. We then verified the action of (±)-kusunokinin compared with neratinibon breast cancer cells (MCF-7). (±)-Kusunokinin exhibited less cytotoxicity on normal L-929 and MCF-7 than neratinib. (±)-Kusunokinin and neratinib had stronger inhibited cell proliferation than siRNA-HER2. Moreover, (±)-kusunokinin decreased Ras, ERK, CyclinB1, CyclinD and CDK1. Meanwhile, neratinib downregulated HER, MEK1, ERK, c-Myc, CyclinB1, CyclinD and CDK1. Knocking down HER2 downregulated only HER2. siRNA-HER2 combination with (±)-kusunokinin suppressed HER2, c-Myc, CyclinB1, CyclinD and CDK1. On the other hand, siRNA-HER2 combination with neratinib increased HER2, MEK1, ERK, c-Myc, CyclinB1, CyclinD and CDK1 to normal levels. We conclude that trans-(±)-kusunokinin may bind HER2 with low affinity and had a different action from neratinib.