A novel lupene derivative from Thymus capitatus possesses an apoptosis-inducing effect via Let-7 miRNA/Cyclin D1/VEGF cascade in the A549 cell line

BMC Complementary Medicine and Therapies · 3 authors, 4 centres

AI SUMMARY

FIDELITY 100%

This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.

AGENT 01 · STRUCTURED SUMMARY

TRACE TO SOURCE

“

TL;DR

All three compounds reduced A549 viability with IC50 values of 0.805 µM, 0.836 µM, and 0.808 µM, respectively, as assessed by MTT assay.

Full summary

578 CHARS

All three compounds reduced A549 viability with IC50 values of 0.805 µM, 0.836 µM, and 0.808 µM, respectively, as assessed by MTT assay. Flow cytometry revealed G2/M cell cycle arrest and a high proportion of cells in late apoptosis, with betulinic acid showing the most pronounced apoptotic effect. RT-qPCR demonstrated that treatment significantly increased mRNA expression of pro-apoptotic markers Bax, CASP-8, and CD95 while downregulating anti-apoptotic Bcl-2. Additionally, let-7 miRNA expression was upregulated and miRNA-21, Cyclin D1, KRAS, and VEGF were downregulated.

STUDY TYPE

other

SPECIALTY

oncology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10577955

A novel lupene derivative from Thymus capitatus possesses an apoptosis-inducing effect via Let-7 miRNA/Cyclin D1/VEGF cascade in the A549 cell line

BMC Complementary Medicine and Therapies

READ THE FULL PAPER

ABSTRACT

Abstract Non-small-cell lung carcinoma (NSCLC) is a type of epithelial lung cancer accounting for about 85% of all lung cancers. In our research, a novel lupene derivative namely acetoxy-lup-5(6), 20(29)-diene (ALUP), as well as two known triterpenes; lupeol (LUP) and betulinic acid (BA) were isolated through the chromatographic purification of the 95% ethanolic extract of Thymus capitatus . Identification of the compounds was carried out by physicochemical properties as well as spectral 1D and 2D NMR analysis. The anti-cancer activity of the three triterpenes was assessed on non-small cell lung cancer cell line; A549 using MTT assay and cell cycle analysis using annexin V/propidium iodide. The molecular mechanism underlying anti-apoptotic effects was determined by analyzing Let-7 miRNA and miRNA-21 expression, the mRNA gene expression level of Bax, CASP-8, CD95, Bcl2, KRAS, VEGF, Cyclin D1 using qRT-PCR. Our results revealed that the three isolated compounds ALUP, LUP, and BA caused cell cycle arrest at the G2/M phase with an increase in the apoptosis which may be attributed to their significant effect on raising Bax, CASP-8, and CD95 and reducing the mRNA expression levels of Bcl-2, KRAS, VEGF, and Cyclin D1 compared to control cells. RT-PCR results showed that the ALUP, LUP, and BA significantly downregulated miRNA-21 expression. Meanwhile, the three compounds caused significant overexpression of Let-7 miRNA. This is the first report on the anti-cancer activity of acetoxy-lup-5(6), 20(29)-diene (ALUP) in reducing the proliferation and differentiation of the A549 cell line through inducing apoptosis. Finally, by targeting the Let-7 miRNA/Cyclin D1/VEGF cascade, acetoxy-lup-5(6), 20(29)-diene could be a potential therapeutic agent for lung cancer. Supplementary Information The online version contains supplementary material available at 10.1186/s12906-023-04201-7. Keywords: Thymus capitatus L., Lupeol derivatives, A549 human non-small cell lung cancer cell line, miRNA-21, Let-7 miRNA

CITATION EXPORT

Nora M Aborehab, Maha M Salama, Shahira M Ezzat. A novel lupene derivative from Thymus capitatus possesses an apoptosis-inducing effect via Let-7 miRNA/Cyclin D1/VEGF cascade in the A549 cell line. BMC Complementary Medicine and Therapies. (2023). https://doi.org/10.1186/s12906-023-04201-7

AUTHORS

3 · 4 CENTRES

Nora M Aborehab, Maha M Salama, Shahira M Ezzat

1Department of Biochemistry, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, 12451 Egypt
2Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr El-Ainy St., Cairo11562, Cairo, 11562 Egypt
3Department of Pharmacognosy, Faculty of Pharmacy, The British University in Egypt, Suez Desert Road, El Sherouk City, Cairo, 11837 Egypt
4Department of Pharmacognosy, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, 12451 Egypt