Meroterpenoids from Daphne genkwa shows promising in vitro antitumor activity via inhibiting PI3K/Akt/mTOR signaling pathway in A549 cells

Ma, Ren-Fen; Liu, Hu; Zhao, Xue-Chun; Shan, Peipei; Sun, Ping; Xue, Jun-Juan; Wei, Guodong; Zhang, Hua

doi:10.1016/j.bioorg.2023.106803

Cited by 8 publications

(8 citation statements)

References 39 publications

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“…Surprisingly, the experimental ECD curves of 1 and 2 showed almost opposite cotton effects (Figure 6). We propose that the observed differences in the ECD cotton effects are primarily due to the benzopyran moiety, rather than the cyclohexanone group, as shown in a previous study, and the ECD method is suitable for the assignment of C-11 [13]. Thus, theoretical ECD calculations were performed using the time-dependent density functional theory (TD-DFT) approach.…”

Section: Resultsmentioning

confidence: 94%

“…The structure of 5 was determined by comparing NMR data [15]. In addition to the five new structures, eight known ascochlorin derivatives, chlorocylindrocarpol (6) [14], grifolic acid (7) [16], ilicicolin A (8) [17], ilicicolin C (9) [18], LL-Z 1272e (10) [19], cylindrochlorin (11) [20], ilicicolin F (12) [19], and ascofuranone (13) [21], were identified by comparison with published NMR data.…”

Section: Resultsmentioning

confidence: 99%

“…A Jasco J1500 spectrometer (Jasco Inc., Tokyo, Japan) was used to obtain the electric circular dichroism (ECD) spectra. The 1D and 2D NMR experiments ( 1 H, 13 C, NOESY, COSY, HSQC, and HMBC) were performed at 300 K in CDCl 3 on a Bruker Avance Neo 600MHz spectrometer (Bruker BioSpin, GmBH) equipped with a Bruker 5 mm PI HR-BBO600s3 Probe. HR-ESIMS was utilized on an LTQ Orbitrap XL mass spectrometer or an Orbitrap Eclipse mass spectrometer (Thermo Fisher Scientific, Waltham, MA, USA) equipped with Xcalibur 4.0 software.…”

Section: General Experimental Proceduresmentioning

confidence: 99%

“…As no ASCs had been previously reported from the target strain, we implemented genomic and GNPS molecular networking to determine if this orphan biosynthetic cluster was indeed responsible for the production of ASCs. Guided by UV absorption and MS data, we identified four undescribed ASCs (1)(2)(3)(4), a newly natural product (5), and eight known ASC analogs (6)(7)(8)(9)(10)(11)(12)(13). Herein, details of their isolation, structure elucidation, and antibiotic activities are described.…”

Section: Introductionmentioning

confidence: 99%

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The Discovery of Acremochlorins O-R from an Acremonium sp. through Integrated Genomic and Molecular Networking

Cui,

Zhou,

Liu

et al. 2024

JoF

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The fermentation of a soil-derived fungus Acremonium sp. led to the isolation of thirteen ascochlorin congeners through integrated genomic and Global Natural Product Social (GNPS) molecular networking. Among the isolated compounds, we identified two unusual bicyclic types, acremochlorins O (1) and P (2), as well as two linear types, acremochlorin Q (3) and R (4). Compounds 1 and 2 contain an unusual benzopyran moiety and are diastereoisomers of each other, the first reported for the ascochlorins. Additionally, we elucidated the structure of 5, a 4-chloro-5-methylbenzene-1,3-diol with a linear farnesyl side chain, and confirmed the presence of eight known ascochlorin analogs (6–13). The structures were determined by the detailed interpretation of 1D and 2D NMR spectroscopy, MS, and ECD calculations. Compounds 3 and 9 showed potent antibacterial activity against Staphylococcus aureus and Bacillus cereus, with MIC values ranging from 2 to 16 μg/mL.

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: General Experimental Proceduresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Discovery of Acremochlorins O-R from an Acremonium sp. through Integrated Genomic and Molecular Networking

Cui,

Zhou,

Liu

et al. 2024

JoF

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“…Pretreatment with autophagy inhibitors restored naringenin-suppressed viability in H1299 cells (Figure 5 D). The phosphatidylinositol 3-kinase/Akt/mTOR and AMPK pathways are crucial regulator of autophagy, proliferation, and survival of cancer cells 67 , 68 . Indeed, we found that naringenin inhibited mTOR phosphorylation and promoted AMPK activation, while pretreatment with ROS scavengers reversed these effects (Figure 5 C and S8B).…”

Section: Discussionmentioning

confidence: 99%

Promotion of ROS-mediated apoptosis, G2/M arrest, and autophagy by naringenin in non-small cell lung cancer

Chang,

Chi,

Chiang

et al. 2024

Int. J. Biol. Sci.

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Background: As lung cancer is the leading cause of cancer death worldwide, the development of new medicines is a crucial endeavor. Naringenin, a flavanone derivative, possesses anti-cancer and anti-inflammatory properties and has been reported to have cytotoxic effects on various cancer cells. The current study investigated the underlying molecular mechanism by which naringenin induces cell death in lung cancer. Methods: The expression of apoptosis, cell cycle arrest, and autophagy markers in H1299 and A459 lung cancer cells was evaluated using a terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL), Western blot, Annexin V/PI stain, PI stain, acridine orange staining, and transmission electron microscopy (TEM). Using fluorescence microscopy, DALGreen was used to observe the degradation of p62, a GFP-LC3 plasmid was used to evaluate puncta formation, and a pcDNA3-GFP-LC3-RFP-LC3ΔG plasmid was used to evaluate autophagy flux. Furthermore, the anti-cancer effect of naringenin was evaluated in a subcutaneous H1299 cell xenograft model. Results: Naringenin treatment of lung cancer cells (H1299 and A459) reduced cell viability and induced cell cycle arrest. Pretreatment of cells with ROS scavengers ( N -acetylcysteine or catalase) suppressed the naringenin-induced cleavage of apoptotic protein and restored cyclin-dependent kinase activity. Naringenin also triggered autophagy by mediating ROS generation, thereby activating AMP-activated protein kinase (AMPK) signaling. ROS inhibition not only inhibited naringenin-induced autophagic puncta formation but also decreased the ratio of microtubule-associated proteins 1A/1B light chain 3 II (LC3II)/LC3I and activity of the AMPK signaling pathway. Furthermore, naringenin suppressed tumor growth and promoted apoptosis in the xenograft mouse model. Conclusion: This study demonstrated the potent anti-cancer effects of naringenin on lung cancer cells, thereby providing valuable insights for developing small-molecule drugs that can induce cell cycle arrest, apoptosis, and autophagic cell death.

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Grifolin Induces Cell Death of Human Lung Cancer A549 Cell Line via Inhibiting KRAS‐Mediated Multiple Signaling Pathways

Zhao,

Ma,

Liu

et al. 2024

Chemistry & Biodiversity

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In the current work, grifolin was obtained from the twigs and leaves of Daphne genkwa for the first time and displayed significant growth inhibition against human lung carcinoma A549 cells. Subsequent in vitro antitumor evaluation revealed that grifolin could induce remarkable cell apoptosis and G0/G1 phase arrest, as well as block cell migration and invasion. In addition, grifolin also disrupted cellular energy metabolism by inducing reactive oxygen species, reducing adenosine triphosphate and mitochondrial membrane potential, and damaging DNA synthesis. Further RNA‐seq analysis demonstrated that treatment of grifolin on A549 cells led to gene enrichment in MAPK, PI3K/Akt and NF‐kB signaling pathways, all of which were inhibited by grifolin according to immunoblotting experiments. Further mechanistical studies disclosed that the expression of a key upstream protein KRAS was also blocked, and the cell death triggered by grifolin could be rescued by a RAS activator ML‐099. Moreover, pretreatment of ML‐099 on A549 cells could reverse the grifolin‐induced downregulation of key proteins in the three aforementioned pathways. These findings indicate that grifolin could induce cell death in A549 cell line by inhibiting KRAS‐mediated multiple signaling pathways.

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Meroterpenoids from Daphne genkwa shows promising in vitro antitumor activity via inhibiting PI3K/Akt/mTOR signaling pathway in A549 cells

Cited by 8 publications

References 39 publications

The Discovery of Acremochlorins O-R from an Acremonium sp. through Integrated Genomic and Molecular Networking

The Discovery of Acremochlorins O-R from an Acremonium sp. through Integrated Genomic and Molecular Networking

Promotion of ROS-mediated apoptosis, G2/M arrest, and autophagy by naringenin in non-small cell lung cancer

Grifolin Induces Cell Death of Human Lung Cancer A549 Cell Line via Inhibiting KRAS‐Mediated Multiple Signaling Pathways

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