Published online May 24, 2021. doi: 10.5306/wjco.v12.i5.342
Peer-review started: January 28, 2021
First decision: March 1, 2021
Revised: March 13, 2021
Accepted: April 26, 2021
Article in press: April 26, 2021
Published online: May 24, 2021
Despite the tremendous improvement in therapeutic approaches, triple-negative breast cancer has poor prognosis. Thymoquinone (TQ), the main constituent of Nigella sativa seeds and royal jelly (RJ), the honeybee secretion fed to honeybee queens, are effective against cancer. However, the anticancer activity of the combination of TQ and RJ against aggressive human breast cancer cells is yet unknown.
To establish novel treatments for breast cancer using natural, relatively non-toxic compounds with significant therapeutic value. We focused on investigating the anticancer activity of TQ and RJ combinations against triple-negative breast cancer.
This study aimed to characterize the anticancer activity of TQ and RJ alone and their combination in vitro against human triple-negative breast cancer.
The inhibitory effect of TQ on triple-negative breast cancer cells was assessed by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Trypan blue exclusion assay was used to evaluate cell viability in response to different treatment conditions. Propidium iodide deoxyribonucleic acid staining followed by flow cytometry was performed to evaluate possible cell cycle regulation and cell death effects. Apoptosis and cell proliferation were determined using immunofluorescence assays for cleaved caspase 3 and Ki67 expression, respectively. The interaction between TQ and RJ and combination indices were evaluated using CompuSyn software.
TQ inhibited MDA-MB-231 breast cancer cell viability in a dose-dependent manner. RJ at low doses was relatively nontoxic to non-tumorigenic FHs 74 Int small intestinal epithelial cells, while at high doses greater toxicity against MDA-MB-231 breast cancer cells was observed. Inhibition of cell viability and cell death effects were more pronounced in response to TQ and RJ combinations compared to each drug alone. The reduction in breast cancer cell viability was mainly due to TQ-mediated caspase 3-dependent apoptosis.
RJ and TQ are relatively non-toxic to normal cells and exhibited pronounced anticancer effects against human metastatic breast cancer. Although our findings demonstrate the potent pro-apoptotic activity of TQ compared to that of RJ, this is the first report of a significant enhancement in TQ’s anticancer activity when combined with RJ.
The reduction in breast cancer cell viability and enhanced cell death effects upon TQ and RJ combinations highlights their potential therapy for human triple-negative breast cancer.