Antitumor and antiangiogenic effects of Tonantzitlolone B, an uncommon diterpene from Stillingia loranthacea

Abrantes, Renata Albuquerque de; Batista, Tatianne Mota; Mangueira, Vivianne Mendes; Sousa, Tatyanna Kélvia Gomes de; Ferreira, Rafael Carlos; Moura, Ana Paula Gomes e; Abreu, Lucas Silva; Alves, Adriano Francisco; Velozo, Eudes da Silva; Batista, Leônia Maria; Silva, Marcelo Sobral da; Tavares, Josean Fechine; Sobral, Marianna Vieira

doi:10.1007/s00210-021-02185-0

Cited by 6 publications

(8 citation statements)

References 38 publications

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“…Some compounds with antitumor activity were found to be significantly upregulated (Table 3). Quercetin [32], strychnopentamine [33], gitogenin [34], rhodioloside [35], liensinine [36], l ‐selenomethionine [37], compactin [38], tonantzitlolone b [39], ginsenoside rg2 [40], campesterol [41], pristimerin derivative [42], cinobufagin [43], and anisomycin [44] have been shown to have antitumor activity. Among them, quercetin, a flavonoid, was the most significantly upregulated.…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, overexpression of Fla1 caused a significant increment in the antitumor activity of the strain, with a reduction in IC 50 from 445 μg/mL to 368 μg/mL and a significant 7‐fold increment in apoptosis. Antitumor‐related compounds have been reported to accumulate in Fla1 overexpressing transformants, for example, quercetin [32], strychnopentamine [33], gitogenin [34], rhodioloside [35], liensinine [36], l ‐selenomethionine [37], compactin [38], tonantzitlolone b [39], ginsenoside rg2 [40], campesterol [41], pristimerin derivative [42], cinobufagin [43] and anisomycin [44], with the flavonoid quercetin being the most significantly upregulated. This result is in contrast to the significant reduction in flavonoid content of AaLaeA OE26 , which also confirms in terms of compound accumulation that AaFla1 is negatively regulated by AaLaeA, and therefore affecting the antitumor activity of the strain.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

AaLaeA targets AaFla1 to mediate the production of antitumor compound in Alternaria alstroemeria

Feng,

Zheng,

Han

et al. 2023

J Basic Microbiol

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Endophytic fungi are an important source of novel antitumor substances. Previously, we isolated an endophytic fungus, Alternaria alstroemeria, from the medicinal plant Artemisia artemisia, whose crude extracts strongly inhibited A549 tumor cells. We obtained a transformant, namely AaLaeAOE26, which completely loses its antitumor activity due to overexpression of the global regulator AaLaeA. Re‐sequencing analysis of the genome revealed that the insertion site was in the noncoding region and did not destroy any other genes. Metabolomics analysis revealed that the level of secondary antitumor metabolic substances was significantly lower in AaLaeAOE26 compared with the wild strain, in particular flavonoids were more downregulated according to the metabolomics analysis. A further comparative transcriptome analysis revealed that a gene encoding FAD‐binding domain protein (Fla1) was significantly downregulated. On the other hand, overexpression of AaFla1 led to significant enhancement of antitumor activity against A549 with a sevenfold higher inhibition ratio than the wild strain. At the same time, we also found a significant increase in the accumulation of antitumor metabolites including quercetin, gitogenin, rhodioloside, liensinine, ginsenoside Rg2 and cinobufagin. Our data suggest that the global regulator AaLaeA negatively affects the production of antitumor compounds via controlling the transcription of AaFla1 in endophytic A. alstroemeria.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

AaLaeA targets AaFla1 to mediate the production of antitumor compound in Alternaria alstroemeria

Feng,

Zheng,

Han

et al. 2023

J Basic Microbiol

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“…Some compounds with anti-tumor activity were found to be significantly up-regulated (Table 3). Quercetin [26], Strychnopentamine [27], Gitogenin [28], Rhodioloside [29], Liensinine [30], L-Selenomethionine [31], Compactin [32], Tonantzitlolone B [33], Ginsenoside Rg2 [34], Campesterol [35], Pristimerin derivative [36], Cinobufagin [37] and Anisomycin [38] have been shown to have antitumour activity. Among them, quercetin, a flavonoid, was the most significantly up-regulated.…”

Section: Fad-binding Domain Proteins Mediate the Production Of Antitu...mentioning

confidence: 99%

AaLaeA targets AaFla1 to mediate the production of antitumor compound in Alternaria alstroemeria

Chen

Wen

Han

et al. 2023

Preprint

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Endophytic fungi are an important source of novel antitumour substances. Previously, we isolated an endophytic fungus, Alternaria alstroemeria, from the medicinal plant Artemisia artemisia, whose crude extracts strongly inhibited A549 tumour cells. We obtained a transformant, namely AaLaeA, which completely loses its antitumour activity due to overexpression of the global regulator AaLaeA. Re-sequencing analysis of the genome revealed that the insertion site was in the non-coding region and did not destroy any other genes. Metabolomics analysis revealed that the level of secondary antitumour metabolic substances was significantly lower in AaLaeA compared to the wild strain, in particular flavonoids were more downregulated according to the metabolomics analysis. A further comparative transcriptome analysis revealed that a gene encoding FAD -binding domain protein (Fla1) was significantly downregulated. On the other hand, overexpression of AaFla1 led to significant enhancement of antitumor activity against A549 with a 7-fold higher inhibition ratio than the wild strain. At the same time, we also found a significant increase in the accumulation of antitumour metabolites including quercetin, gitogenin, rhodioloside, liensinin, ginsenoside Rg2 and cinobufagin. Our data suggest that the global regulator AaLaeA negatively affects the production of antitumour compounds via controlling the transcription of AaFla1 in endophytic Alternaria alstroemeria.

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“…Arg. [229,230]. Tonantzitlolone has been known to have antiproliferative properties against certain cancer cell lines and possess antitumor activity [229,230].…”

Section: Tonantzitlolonementioning

confidence: 99%

“…[229,230]. Tonantzitlolone has been known to have antiproliferative properties against certain cancer cell lines and possess antitumor activity [229,230]. Sourbier et al [110] investigated cytotoxicity targets and mechanisms of action of tonantzitlolone in clear cell RCC.…”

Section: Tonantzitlolonementioning

confidence: 99%

Phytochemicals for the Prevention and Treatment of Renal Cell Carcinoma: Preclinical and Clinical Evidence and Molecular Mechanisms

Bajalia

Azzouz

Chism

et al. 2022

Cancers

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Renal cell carcinoma (RCC) is associated with about 90% of renal malignancies, and its incidence is increasing globally. Plant-derived compounds have gained significant attention in the scientific community for their preventative and therapeutic effects on cancer. To evaluate the anticancer potential of phytocompounds for RCC, we compiled a comprehensive and systematic review of the available literature. Our work was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. The literature search was performed using scholarly databases such as PubMed, Scopus, and ScienceDirect and keywords such as renal cell carcinoma, phytochemicals, cancer, tumor, proliferation, apoptosis, prevention, treatment, in vitro, in vivo, and clinical studies. Based on in vitro results, various phytochemicals, such as phenolics, terpenoids, alkaloids, and sulfur-containing compounds, suppressed cell viability, proliferation and growth, showed cytotoxic activity, inhibited invasion and migration, and enhanced the efficacy of chemotherapeutic drugs in RCC. In various animal tumor models, phytochemicals suppressed renal tumor growth, reduced tumor size, and hindered angiogenesis and metastasis. The relevant antineoplastic mechanisms involved upregulation of caspases, reduction in cyclin activity, induction of cell cycle arrest and apoptosis via modulation of a plethora of cell signaling pathways. Clinical studies demonstrated a reduced risk for the development of kidney cancer and enhancement of the efficacy of chemotherapeutic drugs. Both preclinical and clinical studies displayed significant promise of utilizing phytochemicals for the prevention and treatment of RCC. Further research, confirming the mechanisms and regulatory pathways, along with randomized controlled trials, are needed to establish the use of phytochemicals in clinical practice.

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Antitumor and antiangiogenic effects of Tonantzitlolone B, an uncommon diterpene from Stillingia loranthacea

Cited by 6 publications

References 38 publications

AaLaeA targets AaFla1 to mediate the production of antitumor compound in Alternaria alstroemeria

AaLaeA targets AaFla1 to mediate the production of antitumor compound in Alternaria alstroemeria

AaLaeA targets AaFla1 to mediate the production of antitumor compound in Alternaria alstroemeria

Phytochemicals for the Prevention and Treatment of Renal Cell Carcinoma: Preclinical and Clinical Evidence and Molecular Mechanisms

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