Screening antiproliferative drug for breast cancer from bisbenzylisoquinoline alkaloid tetrandrine and fangchinoline derivatives by targeting BLM helicase
Abstract Background The high expression of BLM (Bloom syndrome) helicase in tumors involves its strong association with cell expansion. Bisbenzylisoquinoline alkaloids own an antitumor property and have developed as candidates for anticancer drugs. This paper aimed to screen potential antiproliferat...
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BMC
2019-10-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-019-6146-7 |
| _version_ | 1818341658966622208 |
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| author | Wangming Zhang Shuang Yang Jinhe Liu Linchun Bao He Lu Hong Li Weidong Pan Yanchao Jiao Zhixu He Jielin Liu |
| author_facet | Wangming Zhang Shuang Yang Jinhe Liu Linchun Bao He Lu Hong Li Weidong Pan Yanchao Jiao Zhixu He Jielin Liu |
| author_sort | Wangming Zhang |
| collection | DOAJ |
| description | Abstract Background The high expression of BLM (Bloom syndrome) helicase in tumors involves its strong association with cell expansion. Bisbenzylisoquinoline alkaloids own an antitumor property and have developed as candidates for anticancer drugs. This paper aimed to screen potential antiproliferative small molecules from 12 small molecules (the derivatives of bisbenzylisoquinoline alkaloids tetrandrine and fangchinoline) by targeting BLM642–1290 helicase. Then we explore the inhibitory mechanism of those small molecules on proliferation of MDA-MB-435 breast cancer cells. Methods Fluorescence polarization technique was used to screen small molecules which inhibited the DNA binding and unwinding of BLM642–1290 helicase. The effects of positive small molecules on the ATPase and conformation of BLM642–1290 helicase were studied by the malachite green-phosphate ammonium molybdate colorimetry and ultraviolet spectral scanning, respectively. The effects of positive small molecules on growth of MDA-MB-435 cells were studied by MTT method, colony formation and cell counting method. The mRNA and protein levels of BLM helicase in the MDA-MB-435 cells after positive small molecule treatments were examined by RT-PCR and ELISA, respectively. Results The compound HJNO (a tetrandrine derivative) was screened out which inhibited the DNA binding, unwinding and ATPase of BLM642–1290 helicase. That HJNO could bind BLM642–1290helicase to change its conformationcontribute to inhibiting the DNA binding, ATPase and DNA unwinding of BLM642–1290 helicase. In addition, HJNO showed its inhibiting the growth of MDA-MB-435 cells. The values of IC50 after drug treatments for 24 h, 48 h and 72 h were 19.9 μmol/L, 4.1 μmol/L and 10.9 μmol/L, respectively. The mRNA and protein levels of BLM helicase in MDA-MB-435 cells increased after HJNO treatment. Those showed a significant difference (P < 0.05) compared with negative control when the concentrations of HJNO were 5 μmol/L and 10 μmol/L, which might contribute to HJNO inhibiting the DNA binding, ATPase and DNA unwinding of BLM helicase. Conclusion The small molecule HJNO was screened out by targeting BLM642–1290 helicase. And it showed an inhibition on MDA-MB-435 breast cancer cells expansion. |
| first_indexed | 2024-12-13T16:02:18Z |
| format | Article |
| id | doaj.art-690eeb605c70498c848601c54cc8c49a |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-13T16:02:18Z |
| publishDate | 2019-10-01 |
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| spelling | doaj.art-690eeb605c70498c848601c54cc8c49a2022-12-21T23:39:08ZengBMCBMC Cancer1471-24072019-10-0119111210.1186/s12885-019-6146-7Screening antiproliferative drug for breast cancer from bisbenzylisoquinoline alkaloid tetrandrine and fangchinoline derivatives by targeting BLM helicaseWangming Zhang0Shuang Yang1Jinhe Liu2Linchun Bao3He Lu4Hong Li5Weidong Pan6Yanchao Jiao7Zhixu He8Jielin Liu9The First Affiliated Hospital of Guizhou University of Chinese MedicineDepartment of Immunology, Basic Medical College, Guizhou Medical UniversityDepartment of Immunology, Basic Medical College, Guizhou Medical UniversityDepartment of Immunology, Basic Medical College, Guizhou Medical UniversityINSERM UMR-S 1165/Paris Diderot 7INSERM UMR 1234/Faculté de Médecine et de Pharmacie, Université de RouenState Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical UniversityGuizhou Entry-exit inspection and quarantine bureauTissue Engineering and Stem Cell Research Center, Guizhou Medical UniversityDepartment of Immunology, Basic Medical College, Guizhou Medical UniversityAbstract Background The high expression of BLM (Bloom syndrome) helicase in tumors involves its strong association with cell expansion. Bisbenzylisoquinoline alkaloids own an antitumor property and have developed as candidates for anticancer drugs. This paper aimed to screen potential antiproliferative small molecules from 12 small molecules (the derivatives of bisbenzylisoquinoline alkaloids tetrandrine and fangchinoline) by targeting BLM642–1290 helicase. Then we explore the inhibitory mechanism of those small molecules on proliferation of MDA-MB-435 breast cancer cells. Methods Fluorescence polarization technique was used to screen small molecules which inhibited the DNA binding and unwinding of BLM642–1290 helicase. The effects of positive small molecules on the ATPase and conformation of BLM642–1290 helicase were studied by the malachite green-phosphate ammonium molybdate colorimetry and ultraviolet spectral scanning, respectively. The effects of positive small molecules on growth of MDA-MB-435 cells were studied by MTT method, colony formation and cell counting method. The mRNA and protein levels of BLM helicase in the MDA-MB-435 cells after positive small molecule treatments were examined by RT-PCR and ELISA, respectively. Results The compound HJNO (a tetrandrine derivative) was screened out which inhibited the DNA binding, unwinding and ATPase of BLM642–1290 helicase. That HJNO could bind BLM642–1290helicase to change its conformationcontribute to inhibiting the DNA binding, ATPase and DNA unwinding of BLM642–1290 helicase. In addition, HJNO showed its inhibiting the growth of MDA-MB-435 cells. The values of IC50 after drug treatments for 24 h, 48 h and 72 h were 19.9 μmol/L, 4.1 μmol/L and 10.9 μmol/L, respectively. The mRNA and protein levels of BLM helicase in MDA-MB-435 cells increased after HJNO treatment. Those showed a significant difference (P < 0.05) compared with negative control when the concentrations of HJNO were 5 μmol/L and 10 μmol/L, which might contribute to HJNO inhibiting the DNA binding, ATPase and DNA unwinding of BLM helicase. Conclusion The small molecule HJNO was screened out by targeting BLM642–1290 helicase. And it showed an inhibition on MDA-MB-435 breast cancer cells expansion.http://link.springer.com/article/10.1186/s12885-019-6146-7BLM helicaseHJNOFluorescence polarizationEMSAMTTRT-PCR |
| spellingShingle | Wangming Zhang Shuang Yang Jinhe Liu Linchun Bao He Lu Hong Li Weidong Pan Yanchao Jiao Zhixu He Jielin Liu Screening antiproliferative drug for breast cancer from bisbenzylisoquinoline alkaloid tetrandrine and fangchinoline derivatives by targeting BLM helicase BMC Cancer BLM helicase HJNO Fluorescence polarization EMSA MTT RT-PCR |
| title | Screening antiproliferative drug for breast cancer from bisbenzylisoquinoline alkaloid tetrandrine and fangchinoline derivatives by targeting BLM helicase |
| title_full | Screening antiproliferative drug for breast cancer from bisbenzylisoquinoline alkaloid tetrandrine and fangchinoline derivatives by targeting BLM helicase |
| title_fullStr | Screening antiproliferative drug for breast cancer from bisbenzylisoquinoline alkaloid tetrandrine and fangchinoline derivatives by targeting BLM helicase |
| title_full_unstemmed | Screening antiproliferative drug for breast cancer from bisbenzylisoquinoline alkaloid tetrandrine and fangchinoline derivatives by targeting BLM helicase |
| title_short | Screening antiproliferative drug for breast cancer from bisbenzylisoquinoline alkaloid tetrandrine and fangchinoline derivatives by targeting BLM helicase |
| title_sort | screening antiproliferative drug for breast cancer from bisbenzylisoquinoline alkaloid tetrandrine and fangchinoline derivatives by targeting blm helicase |
| topic | BLM helicase HJNO Fluorescence polarization EMSA MTT RT-PCR |
| url | http://link.springer.com/article/10.1186/s12885-019-6146-7 |
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