Aconitine linoleate, a natural lipo-diterpenoid alkaloid, stimulates anti-proliferative activity reversing doxorubicin resistance in MCF-7/ADR breast cancer cells as a selective topoisomerase IIα inhibitor

Luan, Shangxian; Gao, Yingying; Liang, Xiaoxia; Zhang, Li; Wu, Qiang; Hu, Yunkai; Yin, Lizi; He, Chao; Liu, Shixi

doi:10.1007/s00210-021-02172-5

Cited by 6 publications

(6 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The studies were evaluated on a scale of 4-7, with an average score of 5.32. Among these studies, 4 ( Zhao et al, 2014 ; Zhang et al, 2017 ; Wu et al, 2018 ; Cheng et al, 2020 ); 10 ( Zeng et al, 2007 ; Rao and Peng, 2010 ; Liu, 2013 ; Ji et al, 2016 ; Ma, 2017 ; Qi et al, 2018b ; Cheng, 2019 ; Wang, 2020 ; Wang et al, 2020 ; Luan et al, 2022 ) studies received 6 points; 18 ( Xu et al, 2008 ; Zhu, 2008 ; Jia and Zhang, 2011 ; Zhang and Wu, 2011 ; Ding et al, 2013 ; Ding, 2014 ; Guan et al, 2015 ; Fan et al, 2016 ; Guan et al, 2017 ; Ma and Yu, 2018 ; Xiong et al, 2018 ; Zhang et al, 2018 ; Shao et al, 2019 ; Zhou et al, 2019 ; Ru et al, 2020 ; Zhang et al, 2020 ; Zou et al, 2021 ; Cai, 2022 ) studies received 5 points; 5 ( Tang and Sun, 1986 ; Yang et al, 2005 ; Ren and Zeng, 2008 ; Wuliji et al, 2008 ; Hao, 2014 ) studies received 4 scores. It is worth noting that all of these studies went through the peer review process before publication.…”

Section: Resultsmentioning

confidence: 99%

“…All of these studies utilized appropriate animal or cellular models and calculated the necessary data. 12 ( Tang and Sun, 1986 ; Yang et al, 2005 ; Zeng et al, 2007 ; Rao and Peng, 2010 ; Liu, 2013 ; Zhao et al, 2014 ; Ma, 2017 ; Zhang et al, 2017 ; Wu et al, 2018 ; Cheng, 2019 ; Cheng et al, 2020 ; Wang, 2020 ) studies mentioned animal welfare regulations, and only 6 ( Ji et al, 2016 ; Zhang et al, 2017 ; Qi et al, 2018b ; Wu et al, 2018 ; Wang et al, 2020 ; Luan et al, 2022 ) studies included a statement regarding potential conflicts of interest.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Antitumor effects and potential mechanisms of aconitine based on preclinical studies: an updated systematic review and meta-analysis

et al. 2023

View full text Add to dashboard Cite

Background: Herbs originating from the Aconitum L. (Ranunculaceae), such as Aconitum carmichaelii Debeaux. (Wutou), Aconitum pendulum Busch. (Tiebangchui), and Aconitum kusnezoffii Reichb. (Caowu), etc. are highly valued for their medicinal properties. The roots and tubers of these herbs are commonly used to treat an array of ailments, including joint pain and tumors. The alkaloids present in them are the primary active components, with aconitine being the most notable. Aconitine has gained attention for its exceptional anti-inflammatory and analgesic properties, as well as its potential as an anti-tumor and cardiotonic agent. However, the exact process through which aconitine hinders the growth of cancerous cells and triggers their programmed cell death remains unclear. Therefore, we have undertaken a comprehensive systematic review and meta-analysis of the current research on the potential antitumor properties of aconitine.Methods: We conducted a thorough search of relevant preclinical studies in databases including PubMed, Web of Science, VIP, WanFang Data, CNKI, Embase, Cochrane Library, and National Center for Biotechnology Information (NCBI). The search was conducted up until 15 September 2022, and the data were statistically analyzed using RevMan 5.4 software. The number of tumor cell value-added, tumor cell apoptosis rate, thymus index (TI), and Bcl-2 gene expression level were the main indicators to be analyzed.Results: After applying the final inclusion criteria, a total of thirty-seven studies, comprising both in vivo and in vitro research were analyzed. The results showed that treatment with aconitine led to a significant reduction in tumor cell proliferation, a noteworthy increase in the rate of apoptosis among tumor cells, a decrease in the thymus index, and a reduction in the expression level of Bcl-2. These results suggested that aconitine could inhibit the proliferation, invasion, and migration abilities of tumor cells by regulating Bcl-2 etc., thereby enhancing the anti-tumor effects.Conclusion: In summary, our present study demonstrated that aconitine effectively reduced tumor size and volume, indicating a strong anti-tumor effect. Additionally, aconitine could increase the expression levels of caspase-3, Bax and other targets. Mechanistically, it may regulate the expression levels of Bax and Bcl-2 through the NF-κB signaling pathway, ultimately inhibiting tumor cell proliferation through autophagy.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Antitumor effects and potential mechanisms of aconitine based on preclinical studies: an updated systematic review and meta-analysis

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Several studies have shown that aconite and its main components can suppress the progression of HCC through multiple pathways [7][8][9]11]. Taipeinine A, which is derived from aconite, has been found to induce apoptosis in the HCC cell line HepG2 [9].…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown that aconite can suppress tumor growth and progression, prevent recurrence and metastasis of multiple cancers, and alleviate pain and other symptoms, including diarrhea and chilliness, in patients undergoing chemotherapy [ 8 , 9 ]. These antitumor effects of aconite can be attributed to inducing apoptosis, inhibiting inflammation, and suppressing epithelial-to-mesenchymal transformation [ 10 , 11 ]. Nevertheless, few studies on the immunoregulation effect of aconite in HCC have been reported.…”

Section: Introductionmentioning

confidence: 99%

The Immunoregulatory Effect of Aconite Treatment on H22 Tumor‐Bearing Mice via Modulating Adaptive Immunity and Natural Killer‐Related Immunity

Wang

Jia³

et al. 2023

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and, in its advanced stages, has a 5-year survival rate of only 3% to 5%. Despite novel mechanisms and treatments being uncovered over the past few years, effective strategies for HCC are currently limited. Previous studies have proven that aconite can suppress tumor growth and progression and prevent the recurrence and metastasis of multiple cancers, but the underlying molecular mechanisms are largely unknown. In this study, different doses of aconite were applied to mice bearing subcutaneous HCC tumors. It was found that aconite had a therapeutic effect on H22 tumor-bearing mice in a dose-dependent manner by reducing tumor volumes and prolonging survival times, which could be attributed to the immunoregulatory effect of aconite. Furthermore, results showed that high-dose administration of aconite could enhance adaptive immunity and natural killer (NK) cell-mediated immunity by regulating the secretion of interferon-γ, upregulating T cells and NK cells, and modulating the expression of the NK cytotoxicity biomarker CD107a and the inhibitory receptor TIGIT. This study revealed a novel mechanism through which aconite exerts antitumor effects, not merely through apoptosis induction pathways, providing more sound evidence that aconite has the potential to be developed into an effective anti-HCC agent.

show abstract

“…By means of molecular docking and topo inhibition tests, it was ascertained that AC functions as a discerning inhibitor of Top IIα. Consequently, AC hinders DNA repair processes and triggers DNA damage, ultimately resulting in the demise of tumor cells ( Luan et al, 2022 ). Finally, autophagy has been widely acknowledged to play a significant role in diverse tumor progression.…”

Section: Pharmacological Activities Of Acmentioning

confidence: 99%

Aconitine and its derivatives: bioactivities, structure-activity relationships and preliminary molecular mechanisms

Zhao,

Tian,

Geng

et al. 2024

Front. Chem.

View full text Add to dashboard Cite

Aconitine (AC), which is the primary bioactive diterpene alkaloid derived from Aconitum L plants, have attracted considerable interest due to its unique structural feature. Additionally, AC demonstrates a range of biological activities, such as its ability to enhance cardiac function, inhibit tumor growth, reduce inflammation, and provide analgesic effects. However, the structure-activity relationships of AC are remain unclear. A clear understanding of these relationships is indeed critical in developing effective biomedical applications with AC. In line with these challenges, this paper summarized the structural characteristics of AC and relevant functional and bioactive properties and the structure-activity relationships presented in biomedical applications. The primary temporal scope of this review was established as the period spanning from 2010 to 2023. Subsequently, the objective of this review was to provide a comprehensive understanding of the specific action mechanism of AC, while also exploring potential novel applications of AC derivatives in the biomedical field, drawing upon their structural characteristics. In conclusion, this review has provided a comprehensive analysis of the challenges and prospects associated with AC in the elucidation of structure-bioactivity relationships. Furthermore, the importance of exploring modern biotechnology approaches to enhance the potential biomedical applications of AC has been emphasized.

show abstract

Aconitine linoleate, a natural lipo-diterpenoid alkaloid, stimulates anti-proliferative activity reversing doxorubicin resistance in MCF-7/ADR breast cancer cells as a selective topoisomerase IIα inhibitor

Cited by 6 publications

References 49 publications

Antitumor effects and potential mechanisms of aconitine based on preclinical studies: an updated systematic review and meta-analysis

Antitumor effects and potential mechanisms of aconitine based on preclinical studies: an updated systematic review and meta-analysis

The Immunoregulatory Effect of Aconite Treatment on H22 Tumor‐Bearing Mice via Modulating Adaptive Immunity and Natural Killer‐Related Immunity

Aconitine and its derivatives: bioactivities, structure-activity relationships and preliminary molecular mechanisms

Contact Info

Product

Resources

About