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Research articles

ScienceAsia 48 (2022): 128-135 |doi: 10.2306/scienceasia1513-1874.2022.014


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


Wantha Jenkhetkana, Arunporn Itharatb, Supranee Kongkhamc, Srisopa Ruangnoob, Treetip Ratanavalachaic,*

 
ABSTRACT:     Among all cancers, the global incidence rate of breast cancer is the highest. Novel chemotherapeutic agents are needed to improve the existing chemotherapy outcomes and to reduce the toxic side effects. 10-hydroxy-2-decenoic acid (10-H2DA), a royal jelly acid, had been reported to have anti-inflammatory, anti-tumor, and anti-metastasis activities. This study aimed to investigate anti-proliferative efficacy and the underlying mechanisms of 10-H2DA co-treatment with doxorubicin (DXR), a chemotherapeutic compound, in MCF-7 breast cancer cells. MTS assay was conducted to determine cell viability. Cell cycle progression and cell apoptosis were detected by flow cytometry. Pivotal protein expressions were determined by Western blot. Results revealed that the 125 µg/ml 10-H2DA co-treatment with the 0.54 µg/ml DXR synergistically and significantly inhibited cancer cell growth up to 79%, compared with the medium control (p < 0.05); it was 1.6-fold higher than the DXR treatment alone. The underlying mechanisms involved extensive suppression of oncoprotein c-MYC/BAX and activation of tumor suppressor The two mechanisms led to G1/S cell cycle arrest, cell apoptosis, and shortened lifespan. The activations of HO-1/BAX and p53/BAX while suppressing NRF2/BAX expression suggested induction of cell ferroptosis. Our findings suggest that the 10-H2DA in adjunct to the DXR is a promising novel candidate for breast cancer treatment via extensive decrease in C-MYC/BAX, increase in p53/BAX, cell cycle arrest, and cell apoptosis. Further in vivo mechanistic studies are necessary to validate its benefits.

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a Division of Biochemistry and Molecular Biology, Faculty of Medicine, Thammasat University, Pathum Thani 12120 Thailand
b Department of Thai Traditional Medicine, Faculty of Medicine, Thammasat University, Pathum Thani 12120 Thailand
c Department of Preclinical Sciences, Division of Biochemistry, Faculty of Medicine, Thammasat University, Pathum Thani 12120 Thailand

* Corresponding author, E-mail: treetip2000@gmail.com

Received 7 Jan 2021, Accepted 14 Sep 2021