Lupeol synergizes with doxorubicin to induce anti-proliferative and apoptotic effects on breast cancer cells.

Abstract

PURPOSE:

Anti-cancer and anti-migration effects of lupeol as a biological pentacyclic triterpenoid were investigated individually and in combination with Doxorubicin (DOX) on MCF-7 and MDA-MB-231 breast cancer cells and human foreskin fibroblasts.

METHODS:

To uncover the anticancer effect of lupeol and the impact of its combination with DOX, cell viability and scratch assays and dual acridine-orange apoptotic staining were performed. Moreover, the expression of proapoptotic caspase-3 and metastasis-related MMP-9 at the mRNA and protein levels was analyzed using qPCR and western blot techniques.

RESULTS:

Lupeol synergistically increased the anti-proliferative effect of DOX with IC50 values of 42.55, 62.24 and 65.9 μM on MCF-7, MDA-MB-231 and HFF cells, respectively. Lupeol reduced the cell migration and lowered the DOX-induced cell migration, significantly (p < 0.05). The number of apoptotic cells elevated significantly (p < 0.05) when cancer cells were treated with the combination of lupeol and DOX. Lupeol individually and in combination with DOX up-regulated the expression of caspase-3. The proposed combination therapy synergized (3-4 fold) the down-regulation of MMP-9 expression in MCF-7 and MDA-MB-231 cells.

CONCLUSION:

Our results indicate that lupeol could be considered as an anticancer agent and anticancer adjuvant in breast cancer-therapy. The anticancer properties of lupeol attribute to its antiproliferative, antimigrative and apoptotic effects.

• Authors: Faezeh Malekinejad, Fatemeh Kheradmand, Mohammad Hassan Khadem-Ansari, Hassan Malekinejad
• Journal: Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences (Daru) Vol. 30 Issue 1 Pg. 103-115 (Jun 2022) ISSN: 2008-2231 [Electronic] Switzerland
• PMID: 35113358 (Publication Type: Journal Article)
• Copyright: © 2022. Springer Nature Switzerland AG.

Chemical References

• Pentacyclic Triterpenes
• Doxorubicin
• Caspase 3
• Matrix Metalloproteinase 9
• lupeol

Topics

• Apoptosis
• Breast Neoplasms (drug therapy, genetics, metabolism)
• Caspase 3 (genetics)
• Cell Line, Tumor
• Cell Proliferation
• Doxorubicin (pharmacology)
• Female
• Humans
• MCF-7 Cells
• Matrix Metalloproteinase 9 (genetics)
• Pentacyclic Triterpenes