Anti-tumor effect of synthetic baicalin-rare earth metal complex drugs on SMMC-7721 cells

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ORIGINAL PAPER

Anti-tumor effect of synthetic baicalin-rare earth metal complex drugs on SMMC-7721 cells Ming Guo . Xiaoyan Gao . Houhui Song . Yi Gu . Peter Christie . Shengchun Wu . Xiaoyue Fan

Received: 2 August 2019 / Accepted: 16 June 2020 Ó Springer Nature B.V. 2020

Abstract Baicalin (BC)-rare earth metal complexes [BMCs (BC-Ce, BC-La, and BC-Y)] were synthesized by a complexation coordination method. A mouse tumor model with SMMC-7721 cells was used to examine BMCs for their anti-tumor activities in vivo. The results show that the three new BMCs, Na3Ce (C21H16O11)310H2O, Na2La (C21H16O11)28H2O, and Na2Y (C21H16O11)26H2O significantly inhibited SMMC-7721 cell proliferation, since the BMCs may induce the tumor apoptosis in a dose-dependent

manner through decreasing cell membrane fluidity and mitochondrial membrane potential depolarization, blocking of the cell cycle at the G2/M phase, and increasing the expression of Bax and reducing the expression of Bcl-2. The effectiveness order of these three BCMs was as follows: BC-Ce [ BC-La [ BCY [ BC. It is concluded that BC-Ce, BC-La, and BCY possess potent anti-tumor effects and may be a novel group of anti-tumor drugs.

Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10653-020-00630-2) contains supplementary material, which is available to authorized users. M. Guo (&)  X. Gao  Y. Gu  X. Fan School of Science, Zhejiang A & F University, Hangzhou 311300, Zhejiang, China e-mail: [email protected] H. Song School of Animal Science and Technology, Zhejiang A & F University, Hangzhou 311300, Zhejiang, China P. Christie  S. Wu (&) School of Environmental and Resource Sciences, Zhejiang A & F University, Hangzhou 311300, Zhejiang, China e-mail: [email protected]

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Environ Geochem Health

Graphic abstract The novel baicalin-rare earth metal complexes (BMC) were synthesized, the antitumor effects of the BMC on SMMC-7721 cell analyzed comprehensively.

Ce Y La Rare earth metal

BC-Ce BC-La

BC-Y IR spectra of BC and BMCs

Complex

UV and Infrared Spectra of BC and BMCs mitochondrial membrane potential The effect of BMCs on cells

Gene expression

SMMC-7721 cell

Keywords Baicalin  Cancer  Flow cytometry  Rare earth element

Introduction Liver cancer is the third cause of death globally after lung and stomach cancers, causing more than 500,000 deaths and about 1 million new cases every year (Bridges et al. 2011; Weiler et al. 2017; Cai et al. 2018). The development and application of novel anti-

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tumor drugs have gained much attention over recent decades (Wolbers 2014; Charbonnel et al. 2015). The chemical compounds used for anti-tumor treatment are limited in clinical therapy due to their side effects (Cui et al. 2016; Liu et al. 2011). On the other hand, natural products have seldom been used due to their low yields and undefined mechanisms. At present, it is necessary to seek new approaches to synthesize efficient anticancer drugs. More specifically, impro