Tumor-suppressing potential of stingless bee propolis in in vitro and in vivo models of differentiated-type gastric adenocarcinoma

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.

Attenuation of carrageenan-induced hind paw edema and plasma TNF-α level by Philippine stingless bee (<i>Tetragonula biroi</i> Friese) propolis

“…Moreover, in our most recent publication, we have identified the existence of several components of this crude propolis extract, which may serve as candidate chemical markers with promising anticancer and anti-inflammatory activity. Based on GC-MS/MS analysis, some of these compounds might possibly constitute a new report at least for the propolis samples [33]. Further studies are being undertaken to verify these speculations.…”

“…Propolis was extracted to obtain a 30% ethanolic fraction with a final concentration of 300 mg/mL as indicated in our earlier publication [31]. Upon phytochemical screening, this crude extract has been found to contain more than 500 chemical constituents, which include carbohydrates, steroids, alkaloids, anthraquinones, phenols, and terpenoids, among others [33]. Moreover, a previous report on propolis samples taken from the same colonies of Philippine stingless bees revealed high amounts of flavonoids and polyphenols i.e.…”

“…Mice were randomly allocated into three (3) treatment groups (n=10/group) namely: Distilled water (negative control); Diclofenac sodium, a non-steroidal antiinflammatory drug (NSAID) given at a concentration of 10mg/kg body weight [35] and served as a positive control; and Propolis, which was administered at a concentration of 100mg/kg body weight [31,33]. Right before use, ethanolic extract of propolis was diluted to several folds of distilled water thereby allowing the vehicle alcohol to fall to negligible concentration (<1%).…”

“…In the Philippines, experimental investigations demonstrating the therapeutic potential of indigenous stingless bee propolis have been greatly limited to our study on its neuroprotective efficacy against ischemic stroke [31] and those from another group detailing its antimicrobial activity against Pseudomonas aeruginosa [32]. More recently, we have illuminated the pronounced specificity in its anticancer activity towards the differentiated subtype of gastric adenocarcinoma but not the diffuse-type [33]. However, no existing evidence has been documented to date concerning its possible regulatory action on the inflammatory process.…”

Stingless Bee Propolis: New Insights for Anticancer Drugs

“…In this context, research on the development of new anticancer drugs has not been limited only to plant substances or molecules. Researchers have investigated the anticancer potential of compounds produced by endophytic fungi [ 11 ], wasp venom peptides [ 12 ], and ant venom [ 13 ], as well as natural products from different bee species, such as honey [ 14 , 15 ] and propolis [ 16 , 17 ].…”