Schisandrin B reverses doxorubicin resistance through inhibiting P-glycoprotein and promoting proteasome-mediated degradation of survivin

Wang, Shengpeng; Wang, Anqi; Shao, Min; Lin, Ligen; Wang, Ying

doi:10.1038/s41598-017-08817-x

Cited by 31 publications

(20 citation statements)

References 51 publications

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“…P-gp inhibitors or substrates can enter the cell from the extracellular compartment to the cytosol via filtration, simple diffusion, or specialized transport. The first step of substrate efflux is the combination of P-gp and the substrates promoted by ATPbinding and hydrolys (Wang et al, 2017a)is. Vanadate trapping and photo-cleavage experiments showed that P-gp contains two active ATPase sites, but only one ATP is hydrolyzed at a time (Hrycyna et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

The Effects of Traditional Chinese Medicine on P-Glycoprotein–Mediated Multidrug Resistance and Approaches for Studying the Herb–P-Glycoprotein Interactions

et al. 2020

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As a member of the ATP-dependent membrane transport proteins, P-Glycoprotein (P-gp) is known to pump substrates out of cells using an ATP-dependent mechanism. The overexpression of P-gp in tumor cells reduces the intracellular drug concentrations, which decreases the efficacy of extensive antitumor drugs and leads to multidrug resistance (MDR) clinically. The combination of anticancer drugs with P-gp inhibitor has been an attractive and promising strategy to reverse MDR in cancer treatment. However, nonspecific or nonselective distribution of P-gp inhibitors to nontarget organs is one of the most fatal shortcomings in clinical application. Thus, there is an urgent need for effective and nontoxic MDR reversal agents, particularly in P-gp-mediated MDR. Traditional Chinese medicine (TCM) natural products may prove less toxic for use in P-gp inhibition to promote MDR reversal. P-gp modulatory effects have been previously demonstrated using selected TCM, including the flavonoid, alkaloid, terpenoid, coumarin, and quinonoid compounds, and some Chinese medicine extracts. Moreover, the approaches for screening active components from TCM are necessary, and these approaches face challenges. At present, the approaches to study the interaction between TCM and P-gp are divided into in vitro, in vivo, and in silico methods. This review will provide an overview and update on the role of TCM in overcoming P-gp-mediated MDR and the approaches to study the interaction between TCM and P-gp. SIGNIFICANCE STATEMENT This review summarized some traditional Chinese medicines identified to have a modulatory effect on P-gp, including flavonoids, alkaloids, terpenoids, coumarins, quinonoid compounds, and some Chinese medicine extracts, and it introduced possible mechanisms. The approaches to study the interaction between TCM and P-gp are divided into in vitro, in vivo, and in silico methods.

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Section: Introductionmentioning

confidence: 99%

The Effects of Traditional Chinese Medicine on P-Glycoprotein–Mediated Multidrug Resistance and Approaches for Studying the Herb–P-Glycoprotein Interactions

et al. 2020

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“… 11 – 13 Various natural products have been shown to be excellent and reliable sources for pharmaceutical development and to be a useful and effective approach for MDR therapies, such as Schisandrin B and annonaceous acetogenins. 14 , 15 …”

Section: Introductionmentioning

confidence: 99%

Kanglaite reverses multidrug resistance of HCC by inducing apoptosis and cell cycle arrest via PI3K/AKT pathway

Yang¹,

Hou²,

Yu³

et al. 2018

OTT

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BackgroundMultidrug resistance (MDR) frequently contributes to the failure of chemotherapeutic treatments in patients diagnosed with hepatocellular carcinoma (HCC). Revealing the molecular mechanism of MDR is indispensable for the development of effective chemotherapeutic drugs.PurposeDue to the low-toxicity modulators to inhibit MDR, we considered that Kanglaite (KLT) is a potential agent for reversing MDR in HCC.Materials and MethodsBEL-7402/5-fluorouracil (5-FU) and HepG2/adriamycin (ADM) were analyzed for cell viability, colony formation assay, cell scratch assay, and cell cycle analysis and apoptosis assay by flow cytometry. The expression of PARP, caspase-3, Bax, Bcl-2, CDC25C, Cyclin B1 and phosphorylation of PTEN, PI3K, and AKT in HepG2/ADM cells were detected by western blotting.ResultsThe proliferation of drug-resistant cell lines BEL-7402/5-FU and HepG2/ADM pretreated with KLT was significantly inhibited when compared with drug alone. KLT could increase the accumulation of ADM in HepG2/ADM cells. In this study, we found that KLT treatment notably reduced cell viability, induced apoptosis and cell cycle arrest in human HepG2/ADM and BEL-7402/5-FU cells, and effectively reversed the MDR by p-glycoprotein (P-gp) inhibition. Moreover, KLT decreased the phosphorylation of AKT and PI3K in KLT-treated HepG2/ADM cells. These data together implied that KLT might reverse drug resistance in HCC by blocking the PI3K/AKT signaling.ConclusionWe demonstrated that KLT reversed MDR of human HCC by inducing apoptosis and cell cycle arrest via the PI3K/AKT signaling pathway.

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“…For instance, various other studies have reported that miR-21-5p was associated with DPP resistance of gastric cancer cells ( 47 , 49 ). Furthermore, the increased resistance to DOX was not entirely due to the elevation of miR-21-5p, and is probably regulated by additional signaling pathways, including the inhibition of P-glycoprotein expression and activity, or via AKT-mediated upregulation of multidrug resistance-associated protein 1 ( 50 , 51 ). All of the above suggests that the mechanism of drug resistance is highly complex, while it is indicated that miR-21-5p may have an important role in the multidrug resistance of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

miR‑21‑5p confers doxorubicin resistance in gastric cancer cells by targeting PTEN and TIMP3

Zhou

Xiang

et al. 2018

Int J Mol Med

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Drug resistance and disease recurrence are major obstacles to the effective treatment of cancer, including gastric cancer (GC). However, the mechanisms of drug resistance remain to be fully elucidated. The present study investigated the roles of microRNA (miR)-21-5p in the doxorubicin (DOX) resistance of GC cells and the underlying mechanisms. miR-21-5p expression levels were identified to be inversely correlated with two well-known tumor suppressor genes, phosphatase and tensin homologue and tissue inhibitor of matrix metalloproteinases 3, and were upregulated in GC cell lines in proportion to their degree of resistance. Suppressing miR-21-5p expression partially sensitized SGC7901/DOX cells to DOX, suggesting that knockdown of miR-21-5p expression may be used as a therapeutic strategy to improve GC cell resistance. Importantly, increased miR-21-5p expression levels at diagnosis were correlated with clinicopathological characteristics including advanced stage and poor prognosis, further implying that a relapse of GC may be a consequence of miR-21-5p upregulation, thus providing evidence for the potential utility of miR-21-5p antagonism to sensitize GC cells to DOX chemotherapy.

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Schisandrin B reverses doxorubicin resistance through inhibiting P-glycoprotein and promoting proteasome-mediated degradation of survivin

Cited by 31 publications

References 51 publications

The Effects of Traditional Chinese Medicine on P-Glycoprotein–Mediated Multidrug Resistance and Approaches for Studying the Herb–P-Glycoprotein Interactions

The Effects of Traditional Chinese Medicine on P-Glycoprotein–Mediated Multidrug Resistance and Approaches for Studying the Herb–P-Glycoprotein Interactions

Kanglaite reverses multidrug resistance of HCC by inducing apoptosis and cell cycle arrest via PI3K/AKT pathway

miR‑21‑5p confers doxorubicin resistance in gastric cancer cells by targeting PTEN and TIMP3

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