Matrine inhibits prostate cancer via activation of the unfolded protein response/endoplasmic reticulum stress signaling and reversal of epithelial to mesenchymal transition

Chang, Junli; Hu, Shaopu; Wang, Wenyi; Li, Yimian; Zhi, Wenlan; Lü, Sheng; Shi, Qi; Wang, Yongjun; Yang, Yanping

doi:10.3892/mmr.2018.9061

Cited by 27 publications

(27 citation statements)

References 51 publications

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“…Matrine has anti-inflammatory [13], anti-viral [14,15], anti-cancer [16], anti-oxidative [17] and anti-apoptotic activities [18]. We found Matrine inhibited the proliferation of PCV2 in PK-15 cells [19], but still its mechanism of action is not evaluated.…”

Section: Introductionmentioning

confidence: 80%

The combined usage of Matrine and Osthole inhibited endoplasmic reticulum apoptosis induced by PCV2

Sun

Wan

et al. 2020

BMC Microbiol

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Background Porcine circovirus type 2 (PCV2) is an important and common DNA virus that infect pig and can cause immunosuppression and induce apoptosis in the infected cells. To escape the host immune system, PCV2 constantly builds up complex mechanisms or mutates genes, and that is why it is difficult to eradicate complex PCV2 infection by relying on vaccines and single compound. At present, there is few literature reports on the effective prevention and treatment of PCV2 infection by a combination of two or more compounds. Previously, we have demonstrated the anti-PCV2 effect of Matrine in vitro, but its mechanism has not been further evaluated. Literatures have proven that Osthole has a variety of pharmacological activities, and we tested the ability of Osthole to inhibit PCV2 replication in cell culture. Therefore, this study explored the synergistic antiviral effect of Matrine combined with Osthole and their synergistic anti-apoptotic mechanism. Results Osthole alone had an anti-PCV2 effect, and then its synergistic anti-PCV2 effect of Osthole and Matrine was better than that of Matrine or Osthole alone as demonstrated by qRT-PCR, IFA and Western blotting results. The anti-apoptotic mechanism of these two compounds by inducing the PERK pathway by PCV2 was elucidated through Annexin V-FITC/PI, JC-1 and Western blotting. Matrine and Osthole combination could inhibit the expression of Cap in Cap-transfected PK-15 cells, thus inhibiting Cap-induced PERK apoptosis. Ribavirin was used as a positive control. Conclusions The combination of Osthole and Matrine had the synergistic effect of anti-PCV2 infection by directly inhibiting the expression of PCV2 Cap protein. The combination of these two compounds also inhibited PERK apoptosis induced by PCV2 Cap protein, possibly by regulating the level of GRP78. The results formed a base for further studies on the mechanism of anti-PCV2 in vivo using Matrine and Osthole combination and developing new anti-PCV2 compounds with Cap and GRP78 as therapeutic targets.

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Section: Introductionmentioning

confidence: 80%

The combined usage of Matrine and Osthole inhibited endoplasmic reticulum apoptosis induced by PCV2

Sun

Wan

et al. 2020

BMC Microbiol

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“…Matrine and Osthole were purchased with a de ned plant origin, chemical structure, concentration and speci c biological activity. Matrine has anti-in ammatory [13], anti-viral [14,15], anti-cancer [16], antioxidative [17] and anti-apoptotic activities [18]. In our previous studies, Matrine inhibited the proliferation of PCV2 in PK-15 cells, but not studied its mechanism of action [19].…”

Section: Introductionmentioning

confidence: 99%

The combined usage of Matrine and Osthole inhibited endoplasmic reticulum apoptosis induced by PCV2

Sun

Wan

et al. 2020

Preprint

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Background: Porcine circovirus type 2 (PCV2) is an important DNA pathogen commonly in pig farms, which can cause immunosuppression and induce apoptosis. To evade clearance by the host immune system, PCV2 constantly builds up complex mechanisms or mutates genes, it is difficult to eradicate complex PCV2 infection by relying on vaccine immunity and one compound. At present, there is no literature report on the effective prevention and treatment of PCV2 infection by the combined a of two or more compounds through multiple pathways and multiple targets. We have previously demonstrated the anti-PCV2 effect of Matrine in vitro, but its mechanism has not been further studied. Many literatures have proved that Osthole has a variety of pharmacological activities. Therefore, this study explored the synergistic antiviral effect of Matrine combined with Osthole and the synergistic anti-apoptosis mechanism in the same pathway and targets.Results: It was first demonstrated that Osthole alone had anti-PCV2 effect and the synergistic anti-PCV2 effect combined with Matrine was better than Matrine and Osthole alone by qPCR, IFA and Western blot results. Subsequently, demonstrated that the reduction of endoplasmic reticulum PERK apoptosis induced by PCV2 was mainly contributed the mechanism of anti-PCV2 using these two extracts by Annexin V-FITC/PI, JC-1 and Western blot results. Finally, it was further demonstrated that Matrine combined with Osthole could inhibit the expression of Cap in cap-transfected PK-15 cells, thus inhibiting Cap-induced PERK apoptosis. In this study, Ribavirin was used as the positive control.Conclusions: It was proved that the synergistic anti-PCV2 effect of Matrine combined with Osthole was significantly better than that of Matrine and Osthole alone. And the two ombined, with Cap and GRP78 as potential targets of anti-PCV2, further inhibited PERK apoptosis induced by PCV2 infection by directly inhibiting the expression of PCV2 Cap protein. The results formed a basis for further studies on the mechanism of anti-PCV2 in vivo using Matrine combined with Osthole and developing new anti-PCV2 compounds with Cap and GRP78 as therapeutic targets.

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“…14 At the same time, a research displayed that MAT restrained prostate carcinoma, which was another kind of carcinoma of the urinary system. 30 Unsurprisingly, we also discovered MAT could restrain cell viability, migratory and invasive potentials but promote apoptosis, and played a protective role in BC cells.…”

Section: Discussionmentioning

confidence: 87%

<p>Matrine Restrains Cell Growth and Metastasis by Up-Regulating LINC00472 in Bladder Carcinoma</p>

Wang

2020

CMAR

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These authors contributed equally to this workPurpose: Bladder Carcinoma (BC) is a malignant carcinoma with a high incidence in masculinity. We preliminarily researched the efficacy and mechanism of matrine (MAT) in T24 and 5637 cells. Patients and Methods: CCK-8, flow cytometry, migration and invasion means were adopted to detect cell viability, apoptosis, migratory and invasive potentials. Moreover, LINC00472 expression was changed via transfection assays and was tested by RT-qPCR. Western blot was used for investigating the levels of CyclinD1, p53, Bcl-2, Bax, pro-Caspase-3, Cleaved-Caspase-3, β-actin, programmed cell death protein 4 (PDCD4) and relate-proteins of cell pathways. Tumor volume and weight were tested via animal experiments. Results: MAT could not affect the growth of SV-HUC-1 cell but MAT promoted tumor cell apoptosis but restrained viability, invasion and migration. Furthermore, LINC00472 was prominently low expressed in BC tissues. MAT positively regulated LINC00472 and transfection with si-00472 could partly reverse the efficacies of MAT. Moreover, MAT enhanced PDCD4 expression by up-regulating LINC00472. Besides, we discovered MAT elevated PTEN but restrained PI3K/AKT proteins. Finally, tumor volume and weight were declined by MAT in vivo via up-regulating LINC00472. Conclusion: MAT restrained cell growth and metastasis but promoted PDCD4 expression by up-regulating LINC00472 via restraining PTEN/PI3K/AKT pathway in BC.

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Matrine inhibits prostate cancer via activation of the unfolded protein response/endoplasmic reticulum stress signaling and reversal of epithelial to mesenchymal transition

Cited by 27 publications

References 51 publications

The combined usage of Matrine and Osthole inhibited endoplasmic reticulum apoptosis induced by PCV2

The combined usage of Matrine and Osthole inhibited endoplasmic reticulum apoptosis induced by PCV2

The combined usage of Matrine and Osthole inhibited endoplasmic reticulum apoptosis induced by PCV2

<p>Matrine Restrains Cell Growth and Metastasis by Up-Regulating LINC00472 in Bladder Carcinoma</p>

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