The synergistic anti-tumor effect of schisandrin B and apatinib

Liu, Hongtao; Xue, Chaojun; Xing, Xiao-Qin; Dong, Songtao; Wang, Linshan; Ding, Cong-Yang; Meng, Ling; Dong, Zhanjun

doi:10.1080/10286020.2019.1645131

Cited by 11 publications

(7 citation statements)

References 22 publications

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“…Apatinib (rivoceranib) is a small molecule that selectively targets VEGFR2. Schisandrin B and apatinib effectively induced apoptosis in gastric cancer cells (53). Schisandrin B and apatinib reduced the levels of MMP9 in gastric cancer cells.…”

Section: Combinatorial Use Of Schisandrin With Therapeutic Agentsmentioning

confidence: 85%

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Regulation of cell signaling pathways by Schisandrin in different cancers: Opting for "Swiss Army Knife" instead of "Blunderbuss"

Lin

Attar

Mobeen³

et al. 2021

Cell Mol Biol (Noisy-le-grand)

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There has been an exponential growth in the field of molecular oncology and cutting-edge research has enabled us to develop a better understanding of therapeutically challenging nature of cancer. Based on the mechanistic insights garnered from decades of research, puzzling mysteries of multifaceted nature of cancer have been solved to a greater extent. Our rapidly evolving knowledge about deregulated oncogenic cell signaling pathways has allowed us to dissect different oncogenic transduction cascades which play critical role in cancer onset, progression and metastasis. Pharmacological targeting of deregulated pathways has attracted greater than ever attention in the recent years. Henceforth, discovery and identification of high-quality biologically active chemicals and products is gaining considerable momentum. There has been an explosion in the dimension of natural product research because of tremendous potential of chemopreventive and pharmaceutical significance of natural products. Schisandrin is mainly obtained from Schisandra chinensis. Schisandrin has been shown to be effective against different cancers because of its ability to inhibit/prevent cancer via modulation of different cell signaling pathways. Importantly, regulation of non-coding RNAs by schisandrin is an exciting area of research that still needs detailed and comprehensive research. However, we still have unresolved questions about pharmacological properties of schisandrin mainly in context of its regulatory role in TGF/SMAD, SHH/GLI, NOTCH and Hippo pathways.

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Section: Combinatorial Use Of Schisandrin With Therapeutic Agentsmentioning

confidence: 85%

“…Schisandrin B and apatinib reduced the levels of MMP9 in gastric cancer cells. Moreover, Schisandrin B improved the efficacy of apatinib by increasing the levels of caspase-9 and Bax in gastric cancer cells (53).…”

Section: Combinatorial Use Of Schisandrin With Therapeutic Agentsmentioning

confidence: 97%

Regulation of cell signaling pathways by Schisandrin in different cancers: Opting for "Swiss Army Knife" instead of "Blunderbuss"

Lin

Attar

Mobeen³

et al. 2021

Cell Mol Biol (Noisy-le-grand)

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“…Additionally, Sch-B enhanced the apoptotic and inhibitory effects of apatinib on gastric cancer cell proliferation. [50] As far as we know, the potentiating effect of Sch-B on panitumumab cytotoxicity has not been reported before.…”

Section: Gene Forward Primer Backword Primer Referencementioning

confidence: 94%

The potential effect of Schisandrin‐B combination with panitumumab in wild‐type and mutant colorectal cancer cell lines: Role of apoptosis and autophagy

Sana-Eldine

Abdelgawad

Kotb

et al. 2023

J Biochem & Molecular Tox

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Panitumumab is an approved monoclonal antibody for the treatment of colorectal cancer (CRC); however, mutations in EGFR signaling pathway resulted in poor response. Schisandrin-B (Sch-B) is a phytochemical that was suggested to protect against inflammation, oxidative stress, and cell proliferation. The present study aimed to investigate the potential effect of Sch-B on panitumumab-induced cytotoxicity in wild-type Caco-2, and mutant HCT-116 and HT-29 CRC cell lines, and the possible underlying mechanisms. CRC cell lines were treated with panitumumab, Sch-B, and their combination. The cytotoxic effect of drugs was determined by MTT assay. The apoptotic potential was assessed in-vitro by DNA fragmentation and caspase-3 activity. Additionally, autophagy was investigated via microscopic detection of autophagosomes and quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR) measurement of Beclin-1, Rubicon, LC3-II, and Bcl-2 expression. The drug pair enhanced panitumumab cytotoxicity in all CRC cell lines where IC50 of panitumumab was decreased in Caco-2 cell line. Apoptosis was induced through caspase-3 activation, DNA fragmentation, and Bcl-2 downregulation. Caco-2 cell line treated with panitumumab showed stained acidic vesicular organelles, contrariwise, all cell lines treated with Sch-B or the drug pair displayed green fluorescence indicating the lack of autophagosomes. qRT-PCR revealed the downregulation of LC3-II in all CRC cell lines, Rubicon in mutant cell lines, andBeclin-1 in HT-29 cell line only. Sch-B at 6.5 µM promoted panitumumab-induced apoptotic cell death, in-vitro, via caspase-3 activation and Bcl-2 downregulation, rather than autophagic cell death. This novel combination therapy against CRC, allows the reduction of panitumumab dose to guard against its adverse effects.

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“…Importantly, Sch.B can enhance panitumumab cytotoxicity in all CRC cell lines and promoted panitumumab-induced apoptotic cell death through caspase-3 activation, DNA fragmentation, and Bcl-2 downregulation [ 20 ]. Sch.B can further target multiple tumor-promoting signaling pathways including epithelial-mesenchymal transition [ 6 , 19 , 21 ] to enhance the effects of other antitumor drugs, for example, apatinib and docetaxel [ 22 , 23 ]. In CRC, Sch.B could induce the SMURF2 protein expression and affected SIRT1 in vitro and in vivo, which negatively correlated each other and may be involved in the antitumor effect [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

A LC-MS/MS Method for Quantifying the Schisandrin B and Exploring Its Intracellular Exposure Correlating Antitumor Effect

Meng

Gao

Chen

et al. 2023

Journal of Analytical Methods in Chemistry

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Schisandrin B (Sch.B) shows antineoplastic activity in colorectal cancer, but the mechanism is still obscure. The intracellular spatial distribution may be helpful in elucidating the mechanism. To investigate the intracellular drug distribution of Sch.B in cancer cells, a simple, rapid, and sensitive ultra-highperformance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was established for the determination of Sch.B in colorectal cancer cells. Warfarin was utilized as an internal standard. The sample pretreatment was carried out with protein precipitation using methanol. The analyte was separated on an Atlantis T3-C18 column (3 μm, 2.1 ∗ 100 mm) using gradient elution with a mobile phase comprised of methanol and 0.2% formic acid in water. The flow rate was 0.4 mL/min. The linear range of Sch.B was 20.0–1000.0 ng/mL with a correlation coefficient (R) more than 0.99. The matrix effect and recovery ranged from 88.01% to 94.59% and from 85.25% to 91.71%; the interday and intraday precision and accuracy, stability, specificity, carryover, matrix effect, and recovery all conformed to the requirements of pharmacopoeia. Cell viability and apoptosis assays demonstrated that Sch.B has an inhibitory effect in a dose-dependent way on HCT116 proliferation and achieved significant suppression at 75 μM (IC50). It was found that in HCT116 cell, nucleus, and mitochondria, exposure levels of Sch.B peaked at 36 h and then decreased, and mitochondria possessed more Sch.B than nucleus. These results may help to elucidate the antitumor effect of Sch.B.

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The synergistic anti-tumor effect of schisandrin B and apatinib

Cited by 11 publications

References 22 publications

Regulation of cell signaling pathways by Schisandrin in different cancers: Opting for "Swiss Army Knife" instead of "Blunderbuss"

Regulation of cell signaling pathways by Schisandrin in different cancers: Opting for "Swiss Army Knife" instead of "Blunderbuss"

The potential effect of Schisandrin‐B combination with panitumumab in wild‐type and mutant colorectal cancer cell lines: Role of apoptosis and autophagy

A LC-MS/MS Method for Quantifying the Schisandrin B and Exploring Its Intracellular Exposure Correlating Antitumor Effect

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