Monitoring the Early Antiproliferative Effect of the Analgesic–Antitumor Peptide, BmK AGAP on Breast Cancer Using Intravoxel Incoherent Motion With a Reduced Distribution of Four b-Values

Doudou, Natacha Raissa; Kampo, Sylvanus; Liu, Huan; Ahmmed, Bulbul; Zeng, Dewei; Zheng, Minting; Aminou, Mohamadou; Wen, Qin; Wang, Shaowu

doi:10.3389/fphys.2019.00708

Cited by 3 publications

(4 citation statements)

References 54 publications

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“…IOD-NaTx showed 62% similarity with BMK-AGAP and both toxins belong to alpha toxin blockers. The IC 50 value of BMK-AGAP on MDA-MB231 cells was reported 50 µM [24], whereas the IC 50 of IOD-NaTx was determined 8 µM in our study.…”

Section: Discussioncontrasting

confidence: 55%

“…IOD-NaTx may also interfere other pathways and molecules in cancer cells. It has been shown that BmK-AGAP downregulates VEGF and TNF-α expression in MDA-MB-231 cells through inactivation of NF-κB signaling mediated by Nav1.5 [22,24]. Thus, inhibition of Nav1.5 by IOD-NaTx may also downregulate VEGF and TNF-α expression via NF-κB inactivation.…”

Section: Discussionmentioning

confidence: 99%

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IOD-NaTx, a scorpion Nav channel toxin induces apoptosis and inhibits growth of highly aggressive breast cancer cells

Khademi

Ayat

Elahian

et al. 2023

Preprint

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Metastatic breast cancer is the most lethal cancer in women that involved various molecular mechanisms. Nav1.5, a voltage-gated sodium channels, is overexpressed in high metastatic breast cancer cells, MDA-MB-231. In this study, we investigated the anti-cancer effect of a new Na+ channel blocker, IOD-NaTx toxin from scorpion. IOD-NaTx toxin contains 66 amino acids that forms three disulfide bonds, converse with other Na+ channels. It was expressed recombinantly in E.coli and purified by nickel affinity chromatography. The cancer cell cytotoxicity was investigated by MTT assay and IC50 of rIOD-NaTx was determined 8µM. Morphological properties of apoptotic cells were observed following toxin treatment. Cell cycle arrest in sub-G1 and increasing amount of p53 mRNA expression also confirmed apoptosis induction in toxin treated cells. IOD-NaTx significantly inhibited mRNA expression of several critical genes involved in breast cancer progression, AKT1, VEGF, LIF, TNF-α. The association of these genes with Nav1.5 channel and PI3K/AKT pathway suggests that IOD-NaTx may affect dufferent pathways through inhibittion of this channel. Fluorescent microscopy analysis showed IOD-NaTx interacte with cancer cells and could penetrate to cells. Therfore, recombinant IOD-NaTx can be considered as an therapeutic cell penetrating peptide for targeting breast cancer cells.

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

IOD-NaTx, a scorpion Nav channel toxin induces apoptosis and inhibits growth of highly aggressive breast cancer cells

Khademi

Ayat

Elahian

et al. 2023

Preprint

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“…In our research, IVIM was set with 10 b values. In previous research, Doudou et al 27 compared 10 and 4 b value parameters and found that there was no significant difference between the 2 groups of parameters. In the study of Fang et al, the authors used the same value of b as in our study 28 …”

Section: Discussionmentioning

confidence: 97%

Correlations between DWI, IVIM, and HIF‐1α expression based on MRI and pathology in a murine model of rhabdomyosarcoma

Yin

Tao

et al. 2022

Magnetic Resonance in Med

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To investigate the correlation between DWI, intravoxel incoherent motion (IVIM), and hypoxia-inducible factor 1-alpha (HIF-1α) expression in a nude mouse model of rhabdomyosarcoma based on imaging and pathological comparisons. Methods: Human rhabdomyosarcoma-derived (RD) cells were inoculated into the right thigh muscle of 20 BALB/c female nude mice. Mice were imaged using 3.0 Tesla MRI system. T 1 -weighted imaging, T 2 -weighted imaging, DWI, and IVIM images were obtained. ADW4.7 (GE Healthcare, ChicagoAQ34, IL, USA) was used for image processing of ADC, D slow , D fast , and f values. All parameter values were independently analyzed by 2 observers. Immunohistochemistry of HIF-1α was performed. We used a specific image-pathology comparison method to ensure correct overlap between the image plane and the pathological section. Mann-Whitney U test or independent sample t test, Pearson or Spearman correlation test, the intragroup correlation coefficient, Kolmogorov-Smirnov test, and receiver operating characteristic curve were used. The correlation between DWI and intravoxel incoherent motion parameter values and HIF-1α expression was determined. Results: There were 10 mice in the low-expression group and 7 in the high-expression group. The ADC and D slow values were negatively correlated with HIF-1α with correlation coefficients of −0.491 and − 0.702 (P = 0.045 and 0.002). The f value positively correlated with HIF-1α expression (r = 0.485, P = 0.048). ADC, D slow , and f were significantly different between the high-HIF-1α expression tumors and the low-HIF-1α expression tumors. ADC showed the best predictive performance among all parameters (area under the curve = 0.652, sensitivity = 83.3%, specificity = 63.6%). Conclusion:The parameter values of DWI and intravoxel incoherent motion can be used to evaluate the expression of HIF-1α in rhabdomyosarcoma. ADC, D slow , and f value showed correlation with the expression of HIF-1α.

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“…et al, 2017 ; Kampo et al, 2019 ). On the other hand, the antiproliferative effect of BmK_AGAP on the early stage of breast cancer has been reported ( Doudou et al, 2019 ; Richard et al, 2020 ). Our study found that Astragaloside IV and PESV have anti-tumor effects in PCa.…”

Section: Discussionmentioning

confidence: 99%

Astragalus–Scorpion Drug Pair Inhibits the Development of Prostate Cancer by Regulating GDPD4-2/PI3K/AKT/mTOR Pathway and Autophagy

You

et al. 2022

Front. Pharmacol.

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Objective: Prostate cancer (PCa) is an epithelial malignancy of the prostate that currently lacks effective treatment. Traditional Chinese medicine (TCM) can play an anticancer role through regulating the immune system, anti-tumor angiogenesis, regulating tumor cell apoptosis, autophagy dysfunction, and other mechanisms. This study attempted to explore the active ingredients and potential mechanism of action of the Astragalus–Scorpion (A–S) drug pair in PCa, in order to provide new insights into the treatment of PCa.Methods: Network pharmacology was used to analyze the A–S drug pair and PCa targets. Bioinformatics analysis was used to analyze the LncRNAs with significant differences in PCa. The expression of LC3 protein was detected by immunofluorescence. CCK8 was used to detect cell proliferation. The expressions of GDPD4-2, AC144450.1, LINC01513, AC004009.2, AL096869.1, AP005210.1, and BX119924.1 were detected by RT-qPCR. The expression of the PI3K/AKT/mTOR pathway and autophagy-related proteins were detected by western blot. LC-MS/MS was used to identify the active components of Astragalus and Scorpion.Results: A–S drug pair and PCa have a total of 163 targets, which were mainly related to the prostate cancer and PI3K/AKT pathways. A–S drug pair inhibited the formation of PCa, promoted the expression of LC3Ⅱ and Beclin1 proteins, and inhibited the expression of P62 and PI3K–AKT pathway proteins in PCa mice. Astragaloside IV and polypeptide extract from scorpion venom (PESV) were identified as the main active components of the A–S drug pair. GDPD4-2 was involved in the treatment of PCa by Astragaloside IV-PESV. Silencing GDPD4-2 reversed the therapeutic effects of Astragaloside IV-PESV by regulating the PI3K/AKT/mTOR pathway.Conclusion: Astragaloside IV-PESV is the main active components of A–S drug pair treated PCa by regulating the GDPD4-2/PI3K–AKT/mTOR pathway and autophagy.

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Monitoring the Early Antiproliferative Effect of the Analgesic–Antitumor Peptide, BmK AGAP on Breast Cancer Using Intravoxel Incoherent Motion With a Reduced Distribution of Four b-Values

Cited by 3 publications

References 54 publications

IOD-NaTx, a scorpion Nav channel toxin induces apoptosis and inhibits growth of highly aggressive breast cancer cells

IOD-NaTx, a scorpion Nav channel toxin induces apoptosis and inhibits growth of highly aggressive breast cancer cells

Correlations between DWI, IVIM, and HIF‐1α expression based on MRI and pathology in a murine model of rhabdomyosarcoma

Astragalus–Scorpion Drug Pair Inhibits the Development of Prostate Cancer by Regulating GDPD4-2/PI3K/AKT/mTOR Pathway and Autophagy

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