Anti‑breast cancer potential of frullanolide from Grangea maderaspatana plant by inducing apoptosis

Abstract

Breast cancer is the leading cause of female mortality worldwide. Although there are several modern treatments for breast cancer, there is a high rate of recurrence for the majority of treatments; therefore, the search for effective anticancer agents continues. The present study aimed to investigate the anti-breast cancer potential of frullanolide, a compound which is isolated and purified from the Grangea maderaspatana plant, for selected human breast cancer cell lines (MCF-7, MDA-MB-468 and MDA-MB-231). The MTT assay was used to assess cytotoxic activity in breast cancer cell lines of treatment with frullanolide at 1.25, 2.5, 5.0, 10.0 and 20.0 µg/ml. Additionally, the apoptotic induction ability of frullanolide at various concentrations [0.5x, 1x and 2x half maximal inhibitory concentration (IC 50)] was investigated by flow cytometry and western blot analysis. Frullanolide exhibited strong anti-breast cancer activity against MDA-MB-468 (IC 50 , 8.04±2.69 µg/ml) and weak cytotoxicity against the MCF-7 (IC 50 , 10.74±0.86 µg/ml) and MDA-MB-231 (IC 50 , 12.36±0.31 µg/ml) cell lines. The IC 50 of frullanolide was high in the human normal epithelial breast cell line (MCF-12A) and mouse fibroblast cell line (L-929). Density plot diagrams revealed that frullanolide induced apoptosis in MCF-7, MDA-MB-468 and MDA-MB-231 cells. Notably, a plausible anticancer mechanism was elucidated via cellular apoptosis by p53-independence in the treated MCF-7 cell line and p53-dependence in the treated MDA-MB-468 and MDA-MB-231 cell lines. In conclusion, the present study demonstrated that frullanolide may exert anticancer activity on breast cancer cell lines by inducing apoptosis. Frullanolide offers a possible novel approach to breast cancer therapy.

Anticancer efficacies of Krameria lappacea extracts against human breast cancer cell line (MCF-7): Role of oxidative stress and ROS generation

“…Therefore, it can be assumed that the differential cytotoxic/anticancer activities of K. lappacea observed in this study may be existence of non-polar compounds in the extracts. Our results are also in agreement with the other reports showing the cytotoxic effects of numerous plant extracts on MCF-7 (human breast cancer cells) ( Khalifa et al, 2013 , Singh et al, 2019 , Chimplee et al, 2019 ). Further, the underlying mechanism of KLH induced MCF-7 cell death was subsequently explored.…”

Anticancer Effects and Molecular Action of 7-α-Hydroxyfrullanolide in G2/M-Phase Arrest and Apoptosis in Triple Negative Breast Cancer Cells

“…Mean differences were statistically analyzed using one-way ANOVA and Bonferroni's multiple comparisons test. IC20, IC50 and IC90: 20%, 50% and 90%-maximal inhibitory concentrations, respectively; SI: selective index; ND: not detected a IC50 (µg/mL): <5 = high cytotoxicity; 5-10 = moderate cytotoxicity; >10-25 = weak cytotoxicity [27,33,34]; b SI: >3 = good selectivity [35,36]; the SI values were calculated by dividing the IC50 (in µ g/mL) in MCF-12A cells (normal breast cells) by the IC50 in breast cancer cells; c p < 0.05, difference in independent IC20, IC50 and IC90 values of cancer cells compared with the corresponding values of the normal cell line (MCF-12A).…”

“…Several SLs, including thapsigargin, artemisinin and parthenolide, have exhibited strong activity against certain types of cancers and their associated stem cells [23]. Furthermore, SLs are commonly extracted from Asteraceae plants, which belong to the same family as G. maderaspatana [23][24][25][26][27]. The compound 7-α-hydroxyfrullanolide (7HF) is extracted from G. maderaspatana and belongs to the eudesmanolide skeleton of SLs.…”

Chitosan-Based Nanoparticles of Targeted Drug Delivery System in Breast Cancer Treatment

“…Several studies have been conducted to find a treatment for breast cancer, but there is no ultimate solution. There is a high recurrence rate for most treatments, so the search for effective anticancer agents continues [ 9 ].…”