Chemopreventive and Chemotherapeutic Effect of Propolis and Its Constituents: A Mini-review

Abstract

Propolis is a bee wax rich in various phytocomponents and traditionally used to treat various ailments. Propolis is reported to possess an array of biological properties including anti-inflammatory, antioxidant, anti-cancer, and anti-diabetic as well as cardioprotective, hepatoprotective, renoprotective, and derma protective activities. A plethora of studies confirmed that propolis is effective against various types of cancer including head and neck, lung, liver, brain (glioma), pancreas, kidney, prostate, skin (melanoma), breast, oral, esophagus, gastric, colorectal, and bladder cancers. However, many researchers have demonstrated that propolis displays potent chemoprotective/chemopreventive or anti-cancer activity against only a few types of cancers like oral, gastrointestinal, dermal (melanoma), breast, and prostate cancers. Therefore, this mini-review only summarizes the chemopreventive/chemotherapeutic activities of propolis and its updated underlying mechanisms. Taken together, propolis displays potent chemoprotective or anti-cancer effect due to the presence of various phytocomponents which contribute to pro-apoptotic, cytotoxic, anti-proliferative (cell cycle arrest), anti-metastatic, anti-invasive, anti-angiogenic and anti-genotoxic or anti-mutagenic properties along with antioxidant, immunomodulatory, and anti-inflammatory functions. Hence, propolis could be used as an adjuvant for treating various cancers along with standard chemotherapeutic drugs. However, many large-scale clinical studies are needed to justify such applications.

Anticancer Activity of Propolis and Its Compounds

“…Some of the published research papers only state the effect of propolis and its components on the inhibition of the proliferation process without penetrating the molecular mechanism [ 9 , 16 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ]. Nevertheless, there are also research results that bring these mechanisms closer.…”

“…It is currently assumed that propolis and its components are reported to modulate cell cycle regulators like cyclin D, cyclin-dependent kinases Cdk-2/4/6, and cyclin-dependent kinase inhibitors, thereby arresting the progression of the cancer cell cycle (G2/M phase), as well as in stage G0/G1, by upregulating p21 and p27 expression [ 49 , 63 , 66 ]. Ethanol-extracted Cameroonian propolis increased the amount of DU145 and PC3 cells in G0/G1 phase, down-regulated cell cycle proteins (CDK1, pCDK1, and their related cyclins A and B) in both DU145 and PC3 cells, and CDK2 and pCDK2 proteins were down-regulated only in PC3 cells [ 67 ].…”

“…It has pro-apoptotic activity through the caspase-3/7 pathway. CAPE significantly increased apoptosis mediated by TRAIL (tumor necrosis factor-related apoptosis ligand inducer) by positive regulation of DR5 (death receptor 5) mediated by CHOP (C/EBP family transcription factor) [ 36 , 38 , 49 , 63 ]. CAPE also affects the apoptotic intrinsic pathway by increasing ROS production and also decreases expression of apoptosis inhibitors such as transporter associated with antigen processing 1 (cTAP-1), baculoviral IAP repeat-containing protein3 (cIAP-2), and X-linked inhibitor of apoptosis protein (XIAP) [ 3 , 63 ].…”

“…CAPE significantly increased apoptosis mediated by TRAIL (tumor necrosis factor-related apoptosis ligand inducer) by positive regulation of DR5 (death receptor 5) mediated by CHOP (C/EBP family transcription factor) [ 36 , 38 , 49 , 63 ]. CAPE also affects the apoptotic intrinsic pathway by increasing ROS production and also decreases expression of apoptosis inhibitors such as transporter associated with antigen processing 1 (cTAP-1), baculoviral IAP repeat-containing protein3 (cIAP-2), and X-linked inhibitor of apoptosis protein (XIAP) [ 3 , 63 ]. Research has also shown that CAPE induces apoptosis by decreasing the levels of proteins related to carcinogenesis, including Akt, glycogen synthase kinase 3 beta (GSK3b), class O forkhead box transcription factor 1 (FOXO1), FOXO3a, NF-kB, S-phase kinase-associated protein 2 (Skp2), and cyclin D1 [ 16 , 101 , 102 ].…”

“…Chrysin also induced endoplasmic reticulum (ER) stress by activating unfolded protein response proteins (UPR) such as PRKR-like ER kinase (PERK), eukaryotic translation initiation factor 2α (eIF2α), and 78 kDa glucose-regulated protein (GRP78). Research results also indicate the involvement of the PI3K/Akt and MAPK pathways in chrysin-induced apoptosis [ 25 , 63 , 104 , 105 ].…”