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The Pro-Apoptotic Activity of Tamarixetin on Liver Cancer Cells Via Regulation Mitochondrial Apoptotic Pathway

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Abstract

Based on the various pharmacological activities of tamarixetin, the present study investigated the cytotoxicity property of tamarixetin in human liver cancer cells including PLC/PRF/5 and HepG2 cells, and their xenografted tumor nude mice. In cells, tamarixetin incubation resulted in the suppression on cell viability; enhanced cell apoptosis rate, LDH release, caspase-3 activation, and reactive oxygen species accumulation; and decreased mitochondrial membrane potential in a dose-dependent manner. Tamarixetin inhibited the growth of PLC/PRF/5- and HepG2-xenografted tumors in BALB/c nude mice after 14-day administration without influencing their bodyweights and organ functions including liver and spleen. Tamarixetin enhanced the expression levels of pro-apoptotic proteins including Bax and cleaved caspase-3 and inhibited the expression levels of anti-apoptotic proteins including Bcl-2 and Bcl-xL in liver cancer cells and their xenografted tumor tissues. Furthermore, tamarixetin significantly suppressed the phosphorylation of ERKs and AKT in both PLC/PRF/5 and HepG2 cells, and tumor tissues. All present data suggest that tamarixetin displays pro-apoptotic properties in liver cancer cells related to the mitochondria apoptotic pathway via regulating the ERKs and AKT signaling.

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All data generated and analyzed during the present study are included in this published article.

Abbreviations

AKT:

Protein kinase B

Bax:

Bcl-2-associated X protein

Bcl-2:

B cell lymphoma 2

Bcl-xL:

B cell lymphoma-extra large

BSA:

Bovine serum albumin

DCFH-DA:

2,7-dichlorofluorescein diacetate

DMEM:

Dulbecco’s modified Eagle’s medium

DMSO:

Dimethyl sulfoxide

ERKs:

Extracellular signal-regulated kinases

FBS:

Fetal bovine serum

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

JC-1:

5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide

LDH:

Lactate dehydrogenase

MAPKs:

Mitogen-activated protein kinases

MMP:

Mitochondrial membrane potential

MPTP:

Mitochondrial permeability transition pores

MTT:

3-(4,5)-dimethylthiahiazo(−z-y1)-3,5-di-pheny-tetrazoliumromide

RIPA:

Radio Immunoprecipitation Assay

ROS:

Reactive oxygen species

TBS-T:

Tris-buffered saline-Tween

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Funding

This work was supported by the National Nature Science Foundation of China (NO. 81501420) and the Special Projects of Cooperation between Jilin University and Jilin Province in P. R. China (SXGJSF2017-1).

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Authors and Affiliations

  1. Cardiovascular Disease Center, First Hospital of Jilin University, Jilin University, Changchun, 130021, Jilin, China

    **g Xu

  2. School of Life Sciences, Jilin University, Changchun, 130012, China

    **nhao Cai, Shanshan Teng, Jiahui Lu, Yulin Zhou & Zhaoli Meng

  3. Department of Stomatology, China-Japan Union Hospital of Jilin University, Jilin University, Changchun, 130033, China

    **aofeng Wang

  4. Department of Translational Medicine, First Hospital of Jilin University, Jilin University, Changchun, 130021, Jilin, China

    Zhaoli Meng

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  1. **g Xu
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Correspondence to **aofeng Wang or Zhaoli Meng.

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The experimental animal study was approved by Jilin University (2017–0110).

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Xu, J., Cai, X., Teng, S. et al. The Pro-Apoptotic Activity of Tamarixetin on Liver Cancer Cells Via Regulation Mitochondrial Apoptotic Pathway. Appl Biochem Biotechnol 189, 647–660 (2019). https://doi.org/10.1007/s12010-019-03033-x

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