Publication: Comparative effects of apis cerana and heterotrigona itama honeys on sensitizing mcf-7 breast cancer cells to doxorubicin
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Date
2026-01
Authors
Xuan, Kam Bao
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Abstract
Breast cancer marked the highest morbidity and mortality rate in females worldwide, including Malaysia. Doxorubicin is an anthracycline commonly used in breast cancer chemotherapy. However, its effectiveness often limited by chemoresistance and adverse effects. Honey, a natural product consisting various phytochemicals with multiple bioactive properties, has the potential as a chemosensitizing agent. This study aimed to determine the half maximal inhibitory concentration (IC50) of Apis cerana (honey bee) honey, Heterotrigona itama (stingless bee) honey and Doxorubicin on MCF-7 breast cancer cells, to identify the combination index (CI) of combination treatments of A. cerana honey with Doxorubicin (AC + Doxo), and H. itama honey with Doxorubicin (HI + Doxo), as well as to compare the sensitizing effect of both combined treatments in metastasis inhibition on MCF-7 breast cancer cells. Honey quality and phytochemical tests were performed to determine the quality of honey and detect the major compounds. The IC50 value of single treatment and CI of combined treatments on MCF-7 breast cancer cells were identified using MTT assay. The sensitizing effects in anti-metastasis of AC + Doxo and HI + Doxo were compared using migration assay. The quality of both honeys is within the acceptable range. Both honeys consist of alkaloids, flavonoids, terpenoids, and saponins, but absence of tannins. Both honeys showed dose-dependent reduction in MCF-7 breast cancer cells, where A. cerana honey (22.98 ± 5.6 mg/mL at 24 hours, 11.78 ± 3.4 mg/mL at 48 hours and 6.92 ± 2.0 mg/mL at 72 hours) has a lower IC50 value than H. itama honey (55.07 ± 23.0 mg/mL at 24 hours, 52.42 ± 11.2 mg/mL at 48 hours and 30.32 ± 5.0 mg/mL at 72 hours). Doxorubicin (0.7562 ± 0.1 μg/mL at 24 hours, 1.066 ± 0.4 μg/mL at 48 hours and 1.098 ± 0.5 μg/mL at 72 hours) has a lower IC50 value than both honeys. A. cerana and H. itama honeys showed synergistic effects on MCF-7 breast cancer cells when combined with Doxorubicin, depending on the concentration of honey. In migration assay, treated MCF-7 breast cancer cells demonstrated slower wound closure compared to the non-treated group. HI + Doxo showed significantly stronger migration inhibitory effect on MCF-7 breast cancer cells than that of AC + Doxo and single treatments. These findings suggested both honeys enhance sensitivity of MCF-7 breast cancer cells to Doxorubicin. A. cerana honey showed stronger cytotoxicity effects than H. itama honey on MCF-7 breast cancer cells, while H. itama honey has greater anti-metastasis synergistic effects on MCF-7 breast cancer cells.