Antiproliferative and Cytotoxic Efficacy of 10-Hydroxy-2-Decenoic Acid, Compared to Doxorubicin, on MCF-7 Breast Cancer Cells
DOI:
https://doi.org/10.48048/tis.2021.409Keywords:
Apoptosis, Cell cycle arrest, C-MYC, 10-hydroxy-2-decenoic acid, NRF2, HO-1Abstract
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
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