Antiproliferative and Cytotoxic Efficacy of 10-Hydroxy-2-Decenoic Acid, Compared to Doxorubicin, on MCF-7 Breast Cancer Cells

Abstract

Exploration of effective chemotherapy is needed for cancer treatment. 10-hydroxy-2-decenoic acid (10-H2DA), a unique fatty acid from royal jelly (RJ), is reported to have antitumor activities. However, its mechanisms remain under-examined. This study investigated the antiproliferative and cytotoxic efficacy of 10-H2DA treatments and their underlying mechanisms, compared to doxorubicin (DXR), on MCF-7 breast cancer cells. The antiproliferative effect was determined using the MTS tetrazolium assay. Cytotoxic activity was performed using a modified MTS assay. Cell cycle progression and cell apoptosis were analyzed by flow cytometry. Pivotal protein expressions were detected by Western blot. Results revealed that 125 µg/mL 10-H2DA treatment significantly inhibited cancer cell growth by 65 %, better than 0.54 µg/mL DXR treatment (48 %), compared to the medium control (p<0.05). The 50 % lethal concentration (LC50) values of 10-H2DA were 190 µg/mL, representing cytotoxic activity. The underlying antiproliferative and cytotoxic mechanisms of 125 µg/mL 10-H2DA treatment demonstrated that it extensively suppressed c-MYC/BAX and slightly activated p53/BAX, leading to G0/G1 cell cycle arrest (decreased cyclin D1 and CDK4) and cell apoptosis (decreased BCL2/BAX). It slightly limited lifespan extension (decreased hTERT/BAX). Nevertheless, it strongly activated HO-1/BAX and NRF2/BAX, possibly inducing chemoresistance and cell invasion later on. Our findings suggested that 10-H2DA treatments induced antiproliferative effects on MCF-7 breast cancer cells via suppression of c-MYC, CDK4, and cyclin D1, leading to cell cycle arrest and cell apoptosis. However, long-term treatment may increase chemoresistance and cell invasion due to induction of antioxidative power, NRF2/BAX, and HO-1/BAX. Therefore, aggressive treatment for a short period would be recommended for using 10-H2DA as a chemotherapeutic compound to prevent chemoresistance and cell invasion. Further long-term in vitro and in vivo studies are necessary to confirm its strength and weakness.
 HIGHLIGHTS
 
 10-hydroxy-2-decenoic acid (10-H2DA), a marker royal jelly acid, effectively inhibited MCF-7 breast cancer cells proliferation and induced cytotoxicity
 The inhibitory mechanisms involved the high suppression of c-MYC, cyclin D1, and CDK4, which induced cell cycle arrest and cell apoptosis
 10-H2DA treatment at proper dose induced high antioxidative potency via activation of NRF2/BAX and HO-1/BAX
 Limitation of 10-H2DA treatment is that it might induce chemoresistance
 
 GRAPHICAL ABSTRACT

Exploring the in vitro potential of royal jelly against glioblastoma and neuroblastoma: impact on cell proliferation, apoptosis, cell cycle, and the biomolecular content

“…55 The 10-HDA stimulated-G0–G1 phase arrest was also reported for MCF-7 cells. 56 Moreover, the G2–M arrest effect of the same organic acid was shown in HepG2 cells, proving our results of the G2–M arrest of GB cells. 40 The difference between the cell cycle arrest phase between SH-SY5Y cells and U373 cells may arise from the variation of RJ-triggered activation or inhibition signal transduction pathways.…”

Synergistic anti-proliferative activities of 10-hydroxy-2- decenoic acid in adjunct to doxorubicin in MCF-7 breast cancer cells

“…The DXR treatment alone significantly decreased cell viability to 52%. Since the 125 µg/ml 10-H2DA treatment alone significantly decreased cell viability to 34.6% [13]; therefore, 125 µg/ml 10-H2DA treatment in combination with the DXR synergistically inhibited cancer cell growth (1.5-fold, compared with the DXR treatment alone). However, the low doses of 0.0125, 0.125, and 1.25 µg/ml 10-H2DA co-treatments tended to have antagonistic effects.…”

“…Our previous studies [13] revealed that the 10-H2DA treatments (1.25, 12.5, and 125 µg/ml) significantly inhibited MCF-7 cell proliferation. The 125 µg/ml 10-H2DA treatment maximally decreased the MCF-7 breast cancer cell viability to 34.6% compared with the medium control and 1.4-fold better than the 0.54 µg/ml DXR treatment.…”