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  • Lin, QingSichuan Univ, Peoples R China; Univ Cambridge, England (författare)

Mechanistic and therapeutic study of novel anti-tumor function of natural compound imperialine for treating non-small cell lung cancer

  • Artikel/kapitelEngelska2020

Förlag, utgivningsår, omfång ...

  • Elsevier,2020
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:liu-162486
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-162486URI
  • https://doi.org/10.1016/j.jep.2019.112283DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Funding Agencies|National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81803447, 81690261]; Fundamental Research Funds for the Central Universities in China [2018SCU12025]; International Visiting Program for Excellent Young Scholars of Sichuan University
  • Ethnopharmacological relevance: Bulbus Fritillaria cirrhosa D. Don (BFC) is a Chinese traditional herbal medicine that has long been used as an indispensable component in herbal prescriptions for bronchopulmonary diseases due to its well-established strong anti-inflammation and pulmonary harmonizing effects. Interestingly, there are few case reports in traditional Chinese medicine available where they found it to contribute in anti-tumor therapies. Imperialine is one of the most favored active substances extracted from BFC and has been widely recognized as an anti-inflammatory agent. Aim of the study: The aim of the current work is to provide first-hand evidences both in vitro and in vivo showing that imperialine exerts anti-cancer effects against non-small cell lung cancer (NSCLC), and to explore the molecular mechanism of this anti-tumor activity. It is also necessary to examine its systemic toxicity, and to investigate how to develop strategies for feasible clinical translation of imperialine. Materials and methods: To investigate anti-NSCLC efficacy of imperialine using both in vitro and in vivo methods where A549 cell line were chosen as in vitro model NSCLC cells and A549 tumor-bearing mouse model was constructed for in vivo study. The detailed underlying anti-cancer mechanism has been systematically explored for the first time through a comprehensive set of molecular biology methods mainly including immunohistochemistry, western blot and enzyme-linked immunosorbent assays. The toxicity profile of imperialine treatments were evaluated using healthy nude mice by examining hemogram and histopathology. An imperialine-loaded liposomal drug delivery system was developed using thin film hydration method to evaluate target specific delivery. Results: The results showed that imperialine could suppress both NSCLC tumor and associated inflammation through an inflammation-cancer feedback loop in which NF-kappa B activity was dramatically inhibited by imperialine. The NSCLC-targeting liposomal system was successfully developed for targeted drug delivery. The developed platform could favorably enhance imperialine cellular uptake and in vivo accumulation at tumor sites, thus improving overall anti-tumor effect. The toxicity assays revealed imperialine treatments did not significantly disturb blood cell counts in mice or exert any significant damage to the main organs. Conclusions: Imperialine exerts anti-cancer effects against NSCLC both in vitro and in vivo, and this previously unknown function is related to NF-kappa B centered inflammation-cancer feedback loop. Imperialine mediated anticancer activity is not through cytotoxicity and exhibit robust systemic safety. Furthermore, the liposome-based system we commenced would dramatically enhance therapeutic effects of imperialine while exhibiting extremely low side effects both on cellular and in NSCLC model. This work has identified imperialine as a promising novel anti-cancer compound and offered an efficient target-delivery solution that greatly facilitate practical use of imperialine.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Qu, MengkeSichuan Univ, Peoples R China (författare)
  • Patra, Hirak,1981-Linköpings universitet,Avdelningen för klinisk kemi,Medicinska fakulteten,Univ Cambridge, England; Univ Cambridge, England(Swepub:liu)hirpa77 (författare)
  • He, ShanshanSichuan Univ, Peoples R China (författare)
  • Wang, LuyaoSichuan Univ, Peoples R China (författare)
  • Hua, XunSichuan Univ, Peoples R China; CQ MEDVT CO LTD, Peoples R China (författare)
  • Xiao, LinyuSichuan Univ, Peoples R China (författare)
  • Fu, YuSichuan Univ, Peoples R China (författare)
  • Gong, TaoSichuan Univ, Peoples R China (författare)
  • He, QinSichuan Univ, Peoples R China (författare)
  • Zhang, LingSichuan Univ, Peoples R China (författare)
  • Sun, XunSichuan Univ, Peoples R China (författare)
  • Zhang, ZhirongSichuan Univ, Peoples R China (författare)
  • Sichuan Univ, Peoples R China; Univ Cambridge, EnglandSichuan Univ, Peoples R China (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of Ethnopharmacology: Elsevier2470378-87411872-7573

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