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28 April 2020 : Animal Research  

Apoptosis Activation in Thyroid Cancer Cells by Jatrorrhizine-Platinum(II) Complex via Downregulation of PI3K/AKT/Mammalian Target of Rapamycin (mTOR) Pathway

KeBin Lu1BCD, Wenjun Wei23BC, Jiaqian Hu23BC, Duo Wen23CDEF, Ben Ma23CD, Wanlin Liu24BC, Yu Wang23ACD*, Zhongwu Lu23AEF

DOI: 10.12659/MSM.922518

Med Sci Monit 2020; 26:e922518

Abstract

BACKGROUND: Thyroid cancer, which is the most common endocrine cancer, has shown a drastic increase in incidence globally over the past decade. The present study investigated the thyroid cancer-inhibitory potential of jatrorrhizine-platinum(II) complex (JR-P(II) in vitro and in vivo.

MATERIAL AND METHODS: The JR-P(II)-mediated cytotoxicity in thyroid carcinoma cells was determined by using MTT assay. Assessment of acetylated histones, tubulin, and DNA repair proteins was made by Western blot assays. Flow cytometry was used for apoptosis and ROS accumulation measurement.

RESULTS: The JR-P(II) suppressed proliferative capacity of SW1736, BHP7-13, and 8305C cells. JR-P(II) treatment markedly promoted expression of acetylated histone H3, H4, and tubulin in a dose-dependent manner. Treatment with JR-P(II) significantly elevated the proportion of cells in sub-G1 and promoted cleaved caspase-3 and -9. In JR-P(II)-treated cells, DCFH-DA fluorescence was much higher relative to control cells. The JR-P(II) treatment consistently suppressed expression of pS6, p-ERK1/2, p-4E-BP1, and p-AKT, and increased p-H2AX expression and suppressed KU70 and KU80 protein levels. The level of RAD51 was repressed in JR-P(II)-treated cells. JR-P(II) administration in mice caused no significant change in body weight, and it inhibited SW1736 tumor growth in mice.

CONCLUSIONS: The JR-P(II) induced cytotoxicity in thyroid cancer cells by inhibiting the mechanism responsible for repair of double-stranded DNA. The in vivo data also revealed that JR-P(II) effectively inhibits thyroid tumor growth by inducing DNA damage. Thus, our results suggest that further evaluation of JR-P(II) as a therapeutic candidate for thyroid cancer is warranted.

Keywords: Antibody-Dependent Cell Cytotoxicity, Chromosomal Proteins, Non-Histone, Parathyroid Neoplasms, Berberine, Platinum, TOR Serine-Threonine Kinases, Thyroid Gland

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750