Genoprotective Effects of Thai Royal Jelly against Doxorubicin in Human Lymphocytes <i>in Vitro</i>

Jenkhetkan, Wantha; Thitiorul, S; Jansom, Chalerm; Ratanavalachai, Treetip

doi:10.1177/1934578x1801300124

Cited by 8 publications

(6 citation statements)

References 24 publications

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“…As shown in Figures 7a and 7b, 10-H2DA treatment at 125 µg/mL decreased the levels of c-MYC, BCL2, h-TERT, BAX, p53, while extensively increasing HO-1 and NRF2 levels. As in our previous publication [33,34], we showed the protein expression levels in a relationship with BAX: c-MYC/BAX, BCL2/BAX, h-TERT/BAX, p53/BAX, HO-1/BAX, and NRF2/BAX (Figure 7c). Such evaluation reflects survival and death in treated cells similar to BCL2/BAX, rheostat regulating life and death [20].…”

Section: Effects Of 10-h2da and Dxr On Regulatory Protein Expressions Detected By Western Blotsupporting

confidence: 84%

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

et al. 2021

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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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Section: Effects Of 10-h2da and Dxr On Regulatory Protein Expressions Detected By Western Blotsupporting

confidence: 84%

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

et al. 2021

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“…6a and 6b). As reported in previous studies [14,15], protein expression levels were better expressed in a relationship with BAX, such as c-MYC/BAX, hTERT/BAX, NRF-2/BAX, and p53/BAX, and protein expressions from live cells versus dead cells were similar to the rheostat ratio, BCL2/BAX [16]. Moreover, BAX could serve as an internal control for comparing different levels of these regulatory proteins.…”

Section: Effects On Ho-1 Nrf2 C-myc Htert P53 Bax and Bcl2 Protein Ex...supporting

confidence: 56%

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

Jenkhetkan¹,

Itharat²,

Kongkham³

et al. 2022

ScienceAsia

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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 antimetastasis 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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“…In our recent work, Nrf2 expression was also found to be upregulated in hepatic tissue of RJ treated mice following Cd intoxication [9]. Moreover, RJ protected lymphocytes against doxorubicin-induced oxidative stress by enhancing Nrf2 and homoxygenase-1 [42]. Additionally, 4-hydroperoxy-2-decenoic acid ethyl ester (HPO-DAEE), a lipid component in RJ, enhanced Nrf2 translocation to the nucleus, activating antioxidant elements, which in turn enhanced the gene expression of the antioxidant and detoxifying enzymes in 6-hydroxydopamine-induced cell death [43].…”

Section: Discussionmentioning

confidence: 99%

Royal Jelly Abrogates Cadmium-Induced Oxidative Challenge in Mouse Testes: Involvement of the Nrf2 Pathway

Almeer

Soliman

Kassab

et al. 2018

IJMS

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The current study examined the efficacy of royal jelly (RJ) against cadmium chloride (CdCl2)-induced testicular dysfunction. A total of 28 Swiss male mice were allocated into four groups (n = 7), and are listed as follows: (1) the control group, who was intraperitoneally injected with physiological saline (0.9% NaCl) for 7 days; (2) the RJ group, who was orally supplemented with RJ (85 mg/kg daily equivalent to 250 mg crude RJ) for 7 days; (3) the CdCl2 group, who was intraperitoneally injected with 6.5 mg/kg for 7 days; and (4) the fourth group, who was supplemented with RJ 1 h before CdCl2 injection for 7 days. Cd-intoxicated mice exhibited a decrease in serum testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels. A disturbance in the redox status in the testicular tissue was recorded, as presented by the increase in lipid peroxidation and nitrate/nitrite levels and glutathione (GSH) depletion. Moreover, the activities of glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and nuclear factor (erythroid-derived 2)-like-2 factor (Nrf2) and their gene expression were inhibited. In addition, interleukin-1ß (IL-1β) and tumor necrosis factor-α (TNF-α) levels were elevated. Furthermore, Cd triggered an apoptotic cascade via upregulation of caspase-3 and Bax and downregulation of Bcl-2. Histopathological examination showed degenerative changes in spermatogenic cells, detachment of the spermatogenic epithelium from the basement membrane, and vacuolated seminiferous tubules. Decreased cell proliferation was reflected by a decrease in proliferating cell nuclear antigen (PCNA) expression. Interestingly, RJ supplementation markedly minimized the biochemical and molecular histopathological changes in testes tissue in response to Cd exposure. The beneficial effects of RJ could be attributed to its antioxidative properties.

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Genoprotective Effects of Thai Royal Jelly against Doxorubicin in Human Lymphocytes in Vitro

Cited by 8 publications

References 24 publications

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

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

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

Royal Jelly Abrogates Cadmium-Induced Oxidative Challenge in Mouse Testes: Involvement of the Nrf2 Pathway

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