Abstract
The protective property of propolis across a wide spectrum of diseases has long been realized, yet the anti-tumor efficacy of this bioactive substance from Philippine stingless bees has remained poorly understood. Here, we showed the tumor-suppressing potential of crude ethanolic extract of Philippine stingless bee propolis (EEP) in in vitro models of gastric cancer highlighting the first indication of remarkable subtype specificity towards differentiated-type human gastric cancer cell lines but not the diffuse-type. Mechanistically, this involved the profound modulation of several cell cycle related gene transcripts, which correlated with the prominent cell cycle arrest at the G0/G1 phase. To reinforce our data, a unique differentiated-type gastric cancer model, A4gnt KO mice, together with age-matched 60 week-old C57BL/6 J mice were randomly assigned to treatment groups receiving distilled water or EEP for 30 consecutive days. EEP treatment induced significant regression of gross and histological lesions of gastric pyloric tumors that consistently corresponded with specific transcriptional regulation of cell cycle components. Also, the considerable p21 protein expression coupled with a marked reduction in rapidly dividing BrdU-labeled S-phase cells unequivocally supported our observation. Altogether, these findings support the role of Philippine stingless bee propolis as a promising adjunct treatment option in differentiated-type gastric cancer.
Highlights
The protective property of propolis across a wide spectrum of diseases has long been realized, yet the anti-tumor efficacy of this bioactive substance from Philippine stingless bees has remained poorly understood
We attempted to explore whether possible anti-cancer efficacy might be included in its repertoire of bioactivities; we carried out a pharmacognostic evaluation of extract of Philippine stingless bee propolis (EEP) from Philippine stingless bees with specific emphasis on its tumor-suppressing potential in in vitro and in vivo models of differentiated-type gastric adenocarcinoma
Means with different letter are significant at P < 0.05 using Analysis of Variance (ANOVA) with Tukey-HSD posttest. i – Wildtype + dH20, ii – Wildtype + EEP, iii – A4gnt KO + dH20, iv - A4gnt KO + EEP
Summary
The protective property of propolis across a wide spectrum of diseases has long been realized, yet the anti-tumor efficacy of this bioactive substance from Philippine stingless bees has remained poorly understood. We showed the tumor-suppressing potential of crude ethanolic extract of Philippine stingless bee propolis (EEP) in in vitro models of gastric cancer highlighting the first indication of remarkable subtype specificity towards differentiated-type human gastric cancer cell lines but not the diffuse-type. Our group was the first to describe that crude EEP from this indigenous bee species could exert potent neuroprotective activity through abrogation of the neurologic deficit and neuronal damage in a rat model of ischemic stroke[27] In this current report, we attempted to explore whether possible anti-cancer efficacy might be included in its repertoire of bioactivities; we carried out a pharmacognostic evaluation of EEP from Philippine stingless bees with specific emphasis on its tumor-suppressing potential in in vitro and in vivo models of differentiated-type gastric adenocarcinoma
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