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

Lin, Qing (författare)
Sichuan Univ, Peoples R China; Univ Cambridge, England
Qu, Mengke (författare)
Sichuan Univ, Peoples R China
Patra, Hirak, 1981- (författare)
Linköpings universitet,Avdelningen för klinisk kemi,Medicinska fakulteten,Univ Cambridge, England; Univ Cambridge, England
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He, Shanshan (författare)
Sichuan Univ, Peoples R China
Wang, Luyao (författare)
Sichuan Univ, Peoples R China
Hua, Xun (författare)
Sichuan Univ, Peoples R China; CQ MEDVT CO LTD, Peoples R China
Xiao, Linyu (författare)
Sichuan Univ, Peoples R China
Fu, Yu (författare)
Sichuan Univ, Peoples R China
Gong, Tao (författare)
Sichuan Univ, Peoples R China
He, Qin (författare)
Sichuan Univ, Peoples R China
Zhang, Ling (författare)
Sichuan Univ, Peoples R China
Sun, Xun (författare)
Sichuan Univ, Peoples R China
Zhang, Zhirong (författare)
Sichuan Univ, Peoples R China
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 (creator_code:org_t)
Elsevier, 2020
2020
Engelska.
Ingår i: Journal of Ethnopharmacology. - : Elsevier. - 0378-8741 .- 1872-7573. ; 247
Relaterad länk:
https://urn.kb.se/re...
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https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

Imperialine; Bulbus Fritillaria cirrhosa D. Don; Inflammation-cancer translation; Non-small cell lung cancer; NB-kappa B; Low toxicity; NSCLC-targeting liposomes

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