Publication: Anticancer effects of apis cerana and heterotrigona itama honeys on temozolomide-resistant glioblastoma cells
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Date
2025-01
Authors
Hui, You Ying
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Abstract
Glioblastoma is characterized by high aggressiveness and poor prognosis with median survival rate of less than 15 months. Due to the complexity of surgery to remove whole tumour and rapid development of chemoresistance towards temozolomide (TMZ), apitherapy using honey emerges as potential alternative treatment for glioblastoma due to its rich phenolic compounds with high antioxidant properties. However, the difference between Apis cerana honey and Heterotrigona itama honey for anti-glioblastoma effects has not been extensively studied. In this study, the phytochemical composition of A. cerana and H. itama honey were compared using phytochemical screening test and fourier transform infrared spectroscopy (FTIR) analysis. Their antioxidant capabilities were also compared using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Then, the half-maximal inhibitory concentration (IC50) values of both honeys on TMZ-resistant glioblastoma cell line (DBTRG-05MG cells) were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while the analysis of cancer invasiveness and recurrence were determined through scratch assay and clonogenic assay respectively. After that, gene expressions between both honey-treated DBTRG-05MG cells were compared using quantitative reverse transcription polymerase chain reaction (qRT-PCR) to elucidate their effects towards apoptosis (MDM2 gene), metastasis (WNT5A gene) and chemoresistance (YTHDF2 gene). The analysis revealed that A. cerana honey contained higher levels of alkaloid and saponin as compared to H. itama honey, which contributed to its higher antioxidant activity as evidenced via the DPPH assay. This data was also supported by its lower IC50 value (130.5 ± 33.1 mg/mL) than H. itama honey (185.8 ± 27.6 mg/mL) in 72-hour treatment on DBTRG-05MG cells. In contrast, H. itama honey contained higher levels of flavonoid than A. cerana honey. Both honeys shared similar functional groups as indicated in FTIR analysis. A. cerana honey exerted strong inhibitory effect towards invasiveness and migration of DBTRG-05MG cells with its lowest closure percentage up to 72 hours while H. itama honey exerted strong prophylactic effect towards recurrence of DBTRG-05MG cells with its lowest colony number formed. However, there was no significant difference in MDM2, WNT5A and YTHDF2 expressions between honey-treated DBTRG-05MG cells. These findings suggest that A. cerana honey could be more effective in killing TMZ-resistant glioblastoma cells while H. itama honey could be more effective in preventing glioblastoma recurrence. The anticancer effect of each phytochemical in both honeys should be further investigated in future for better elucidation towards apoptotic, metastasis and chemoresistance mechanisms
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