Dual effects of isoflavonoids from Pueraria lobata roots on estrogenic activity and anti-proliferation of MCF-7 human breast carcinoma cells

Ahn, Soo-Yeon; Jo, Mun Seok; Lee, Dahae; Baek, Seon-Eun; Baek, Jin Wook; Yu, Jae Sik; Jo, Jeyun; Yun, Hwayoung; Kang, Ki Sung; Yoo, Jeong-Eun; Kim, Ki‐Hyun

doi:10.1016/j.bioorg.2018.10.017

Cited by 34 publications

(22 citation statements)

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“…As part of ongoing projects to identify structurally and/or biologically novel compounds from natural sources [13][14][15][16][17], we investigated the active compounds from P. lobata root that have both estrogen-like and anti-breast cancer cell proliferative activities. We used the bioactivity-guided isolation approach employed in a recent report that demonstrated that genistein from P. lobata root has estrogen-like effects dependent on estrogen receptor (ER) pathway activation, and anti-proliferative effects mediated by the apoptosis pathway in MCF-7 breast cancer cells [18]. These findings prompted us to investigate other potential bioactive components from P. lobata roots.…”

Section: Introductionmentioning

confidence: 99%

Lobatamunsolides A–C, Norlignans from the Roots of Pueraria lobata and their Nitric Oxide Inhibitory Activities in Macrophages

Lee

et al. 2019

Biomolecules

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Phytochemical investigation of the methanol (MeOH) extract of Pueraria lobata roots, known as “kudzu”, combined with liquid chromatography/mass spectrometry (LC/MS)-based analysis, resulted in the identification of four norlignans (1–4), including three new norlignans, lobatamunsolides A–C (1–3), and five known isoflavonoids (5–9). The structures of the new compounds were elucidated by a combination of spectroscopic methods, including 1D and 2D nuclear magnetic resonance (NMR) and high resolution (HR)-electrospray ionization mass spectrometry (ESIMS), and their absolute configurations were determined by chemical reaction and quantum chemical electronic circular dichroism (ECD) calculations. The isolated compounds (1–9) were evaluated for their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Compound 9 displayed the strongest NO inhibitory effect and compound 2 showed a weak effect. The potential mechanism of the effect of compound 9 was investigated by analysis of its molecular docking on the active site of inducible nitric oxide synthase (iNOS), which showed the potential interactions of compound 9 with key amino acid residues and the heme cofactor of iNOS. The mechanism as the inhibition of transcriptional iNOS protein expression was confirmed by western blotting experiments.

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Section: Introductionmentioning

confidence: 99%

Lobatamunsolides A–C, Norlignans from the Roots of Pueraria lobata and their Nitric Oxide Inhibitory Activities in Macrophages

Lee

et al. 2019

Biomolecules

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“…The choice of the natural Chinese herbal molecule Scutellarin. There are many Chinese herbs that have therapeutic effects on the cancer, for example, Huang Qin [33], Ge Gen [38], Bai Shu [39], Ban Zhi Lian [40] and Gan Cao [41]. Therefore, based on the structural characteristics of Compound 9, we tried to explore potential inhibitors that have a similar conformation to compound 9 from TCMS, which has three carbon rings in a line in terms of a 2D chemical structure as shown in Table 1.…”

Section: Resultsmentioning

confidence: 99%

Structural Insight into the Interactions between Structurally Similar Inhibitors and SIRT6

Zhao

Zhu

Wang

et al. 2020

IJMS

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Sirtuin 6 (SIRT6) is an NAD+-dependent deacetylase with a significant role in 20% of all cancers, such as colon cancers and rectal adenocarcinoma. However, there is currently no effective drug for cancers related to SIRT6. To explore potential inhibitors of SIRT6, it is essential to reveal details of the interaction mechanisms between inhibitors and SIRT6 at the atomic level. The nature of small molecules from herbs have many advantages as inhibitors. Based on the conformational characteristics of the inhibitor Compound 9 (Asinex ID: BAS13555470), we explored the natural molecule Scutellarin, one compound of Huang Qin, which is an effective herb for curing cancer that has been described in the Traditional Chinese Medicine (TCMS) library. We investigated the interactions between SIRT6 and the inhibitors using molecular dynamics (MD) simulations. We illustrated that the structurally similar inhibitors have a similar binding mode to SIRT6 with residues-Leu9, Phe64, Val115, His133 and Trp188. Hydrophobic and π-stacking interactions play important roles in the interactions between SIRT6 and inhibitors. In summary, our results reveal the interactive mechanism of SIRT6 and the inhibitors and we also provide Scutellarin as a new potential inhibitor of SIRT6.Our study provides a new potential way to explore potential inhibitors from TCMS.Int. J. Mol. Sci. 2020, 21, 2601 2 of 15 cancers and rectal adenocarcinoma, according to the Cancer Genome Atlas database [17]. Crystal structure of SIRT6 (PDB code 3K35) [23,24] includes the hydrophobic channel, the Rossman fold and the small domain shown in Figure S1A [25]. The Rossman fold is one of the most common and widely distributed super-secondary structures. The dinucleotide such as FAD, NAD and NADP can bind in the domain [26]. There is a long hydrophobic-channel pocket that binds the small molecules [27].Probing potential inhibitors has become essential for the development of cancer drug design [4,28,29]. Several potential inhibitors of SIRT6 have been reported, such as Compound 9 [3,30], trichostatin A [23] and inhibitors with a salicylate-linked structure [31]. Parenti et al. synthesized three (SYN17739303, BAS13555470 or Compound 9 and BAS00417531) potential inhibitors for SIRT6 [30]. Interestingly we found that the three inhibitors have similar chemical structure. The structures of these inhibitors can give insight into the direction of the design of improved inhibitors. However, the mechanism of interactions between the inhibitors and SIRT6 is still elusive. The relationship between the interactions and the bioactivity of SIRT6 is also not clear.Small molecules from herbs have many advantages as inhibitors. For example, herbal medicine has low toxicity and can be easily absorbed and easily expelled from the body. In this investigation, we therefore sought to probe structure-based inhibitors similar to Compound 9 [30] from Traditional Chinese Medicines (TCMS). Scutellarin is one compound of Scutellaria baicalensis Georgi, named Huang Qin in TCMS. It has been reported that ...

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“…To detect apoptotic cell death, the annexin V Alexa Fluor 488 binding assay was performed in accordance with the manufacturer's instructions. The cells were treated with either 0.5% DMSO (control), or the indicated concentrations of sample (L. cuneata methanolic extract fractions or isolated compounds 1-9) dissolved in 0.5% DMSO for 24 h, as described in the literatures [36][37][38]. The cells were harvested and prepared to the same concentration of cells for each individual group.…”

Section: Cell Staining With Annexin Vmentioning

confidence: 99%

Aviculin Isolated from Lespedeza cuneata Induce Apoptosis in Breast Cancer Cells through Mitochondria-Mediated Caspase Activation Pathway

Lee

et al. 2020

Molecules

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The global incidence of breast cancer has increased. However, there are many impediments to the development of safe and effective anticancer drugs. The aim of the present study was to evaluate the effect of aviculin isolated from Lespedeza cuneata (Dum. Cours.) G. Don. (Fabaceae) on MCF-7 human breast cancer cells and determine the underlying mechanism. Using the bioassay-guided isolation by water soluble tetrazolium salt (WST-1)-based Ez-Cytox assay, nine compounds (four lignan glycosides (1–4), three flavonoid glycosides (5–7), and two phenolic compounds (8 and 9)) were isolated from the ethyl acetate (EA) fraction of the L. cuneata methanolic extract. Of these, aviculin (2), a lignan glycoside, was the only compound that reduced metabolic activity on MCF-7 cells below 50% (IC50: 75.47 ± 2.23 μM). The underlying mechanism was analyzed using the annexin V Alexa Fluor 488 binding assay and Western blotting. Aviculin (2) was found to induce apoptotic cell death through the intrinsic apoptosis pathway, as indicated by the increased expression of initiator caspase-9, executioner caspase-7, and poly (ADP-ribose) polymerase (PARP). Aviculin (2)-induced apoptotic cell death was accompanied by an increase in the Bax/Bcl-2 ratio. These findings demonstrated that aviculin (2) could induce breast cancer cell apoptosis through the intrinsic apoptosis pathway, and it can therefore be considered an excellent candidate for herbal treatment of breast cancer.

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Dual effects of isoflavonoids from Pueraria lobata roots on estrogenic activity and anti-proliferation of MCF-7 human breast carcinoma cells

Cited by 34 publications

References 29 publications

Lobatamunsolides A–C, Norlignans from the Roots of Pueraria lobata and their Nitric Oxide Inhibitory Activities in Macrophages

Lobatamunsolides A–C, Norlignans from the Roots of Pueraria lobata and their Nitric Oxide Inhibitory Activities in Macrophages

Structural Insight into the Interactions between Structurally Similar Inhibitors and SIRT6

Aviculin Isolated from Lespedeza cuneata Induce Apoptosis in Breast Cancer Cells through Mitochondria-Mediated Caspase Activation Pathway

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