Water-soluble propolis and bee pollen of Trigona spp. from South Sulawesi Indonesia induce apoptosis in the human breast cancer MCF-7 cell line

Bee products are best known as one of the beneficial natural products providing multiple pharmacological effects, such as antimicrobial, antiviral, anti-inflammatory and anticancer effects. The present study aimed to identify potent products derived from the stingless bee Trigona spp. from Luwu Utara (South Sulawesi, Indonesia), focussing on the water-soluble extract of propolis and bee pollen, against the proliferation of the human breast cancer MCF-7 cell line. The results from DPPH (2,2-diphenyl-1-picrylhydrazyl) method of antioxidant assay revealed that water-soluble propolis and bee pollen had high antioxidant activity, with half-maximal effective concentrations against DPPH radicals of 1.3 and 0.4 mg/ml, respectively. Additionally, water-soluble propolis and bee pollen exhibited a significant antiproliferative activity in MCF-7 cells, with IC50 values of 10.8±0.06 and 18.6±0.03 mg/ml, respectively (P<0.05). Significant cytotoxic effects were observed after 24 h of treatment via microscopic and flow cytometric analysis, where a morphological change toward late apoptosis was observed. By contrast, honey had low antioxidant activity and no antiproliferative effect in MCF-7 cells. The water-soluble propolis also exerted its antiproliferative effect in the human keratinocyte HaCaT cell line. The antiproliferative activity was similar (P>0.05) at 24 and 48 h of treatment, with IC50 at 2.7±0.06 mg/ml and <0.4 mg/ml, respectively. Notably, bee pollen was less toxic to HaCaT cells after 24 h of treatment than the water-soluble propolis, with IC50>50 mg/ml. Its antiproliferative activity was significantly increased after 48 h of treatment, with IC50 at 9.6±0.07 mg/ml (P<0.05). In addition, similar to other poplar propolis, the high-performance liquid chromatography-ultraviolet and electrospray ionisation mass spectrometry analyses revealed that caffeic acid phenethyl ester was not the main bioactive compound of the samples examined. Furthermore, two major proteins (between ~50 and 75 kDa) were identified in the water-soluble propolis and bee pollen. The present results suggested that water-soluble propolis and bee pollen may have the potential to be elaborated further as a breast anticancer therapy.

[1]  A. Rohman,et al.  Indonesian wild honey authenticity analysis using attenuated total reflectance-fourier transform infrared (ATR-FTIR) spectroscopy combined with multivariate statistical techniques , 2020, Heliyon.

[2]  H. Kitamura Effects of Propolis Extract and Propolis-Derived Compounds on Obesity and Diabetes: Knowledge from Cellular and Animal Models , 2019, Molecules.

[3]  K. Gwoździński,et al.  Anticancer Activity of Natural Compounds from Plant and Marine Environment , 2018, International journal of molecular sciences.

[4]  Irnawati Irnawati Penetapan Kadar Vitamin C Dan Uji Aktifitas Antioksidan Sari Buah Songi (Dillenia Serrata Thunb.) Terhadap Radikal Dpph (Diphenylpicrylhydrazyl) , 2017 .

[5]  N. Othman,et al.  The anti-cancer effects of Tualang honey in modulating breast carcinogenesis: an experimental animal study , 2017, BMC Complementary and Alternative Medicine.

[6]  Leslie Z Benet,et al.  Classification of natural products as sources of drugs according to the biopharmaceutics drug disposition classification system (BDDCS). , 2016, Chinese journal of natural medicines.

[7]  P. Nigam,et al.  Manuka Honey-induced Cytotoxicity against MCF7 Breast Cancer Cells is Correlated to Total Phenol Content and Antioxidant Power , 2016 .

[8]  M. Savitskaya,et al.  Mechanisms of apoptosis , 2015, Biochemistry (Moscow).

[9]  Marius Raica,et al.  The Story of MCF-7 Breast Cancer Cell Line: 40 years of Experience in Research. , 2015, Anticancer research.

[10]  D. Dezmirean,et al.  Caffeic Acid Phenethyl Ester (CAPE) in Romanian Propolis , 2014 .

[11]  S. Nathanson,et al.  Pathogenesis, prevention, diagnosis and treatment of breast cancer. , 2014, World journal of clinical oncology.

[12]  C. Chanchao,et al.  In vitro cytotoxicity of Indonesian stingless bee products against human cancer cell lines. , 2014, Asian Pacific journal of tropical biomedicine.

[13]  G. Amidon,et al.  The Biopharmaceutics Classification System: subclasses for in vivo predictive dissolution (IPD) methodology and IVIVC. , 2014, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[14]  G. Murtaza,et al.  Caffeic Acid Phenethyl Ester and Therapeutic Potentials , 2014, BioMed research international.

[15]  A. A. Siddiqui,et al.  Role of Natural Products in Drug Discovery Process , 2014 .

[16]  T. Salameh,et al.  Low and high voltage electrochemotherapy for breast cancer: an in vitro model study , 2014 .

[17]  O. O’Connor,et al.  Propolis and its Active Component, Caffeic Acid Phenethyl Ester (CAPE), Modulate Breast Cancer Therapeutic Targets via an Epigenetically Mediated Mechanism of Action. , 2013, Journal of cancer science & therapy.

[18]  K. Paknikar,et al.  Anticancer Activity of Indian Stingless Bee Propolis: An In Vitro Study , 2013, Evidence-based complementary and alternative medicine : eCAM.

[19]  B. Niknafs Induction of apoptosis and non-apoptosis in human breast cancer cell line (MCF-7) by cisplatin and caffeine. , 2011, Iranian biomedical journal.

[20]  Donald Wlodkowic,et al.  Flow cytometry-based apoptosis detection. , 2009, Methods in molecular biology.

[21]  K. Hahn,et al.  Characterization of Morphological and Cytoskeletal Changes in MCF10A Breast Epithelial Cells Plated on Laminin-5: Comparison with Breast Cancer Cell Line MCF7 , 2001, Cell communication & adhesion.

[22]  M. C. Marcucci,et al.  Propolis: recent advances in chemistry and plant origin , 2000 .

[23]  C. García-Viguera,et al.  Study of Canadian Propolis by GC-MS and HPLC , 1993 .