Effects of olive oil-based propolis, caffeic acid phenethyl ester, and methylprednisolone on differentiation of human acute myeloid leukemia cells

Hamide Doğan; Ahmet Ata Ozcimen; Sibel Silici

Effects of olive oil-based propolis, caffeic acid phenethyl ester, and methylprednisolone on differentiation of human acute myeloid leukemia cells

Abstract

Leukemia, originating from the hematopoietic system, is a malignant disease for the treatment of which various glucocorticoids are used. The use of natural products alongside conventional therapy has focused on increasing drug-drug interactions and reducing potential side effects. Based on the idea that propolis and caffeic acid phenethyl ester (CAPE) can stimulate cancer cells to differentiation and enhance the effect of chemotherapeutic drugs, we conducted this study. In this study, we investigated whether the synergistic effect of olive oil-based propolis and CAPE is effective with metylprednisolone (MP), which is used for supportive therapy in AML. In the study, OEP (Olive Oil- Based Propolis), CAPE, MP and their combinations were applied to HL -60 cells for 1-3 days. Then, CD11b, CD14 and CD68 antigens were detected on HL -60 cells using flow cytometry techniques to determine the cellular differentiations. As a result, HL -60 cells were found to be significantly directed to CD11b differentiation. OEP and CAPE will enhance the effect of chemotherapy by differentiating cells and ensure treatment completion by minimizing damage to normal tissues and cells.

Keywords

References

Cho HJ, Lee J, Yoon SR, Lee HG, Jung H. Regulation of hematopoietic stem cell fate and malignancy. Int J Mol Sci. 2020; 21: 4780. [CrossRef]
Wilson A, Trumpp A. Bone-marrow haematopoietic-stem-cell niches. Nat Rev Immunol. 2006; 6(2): 93-106. [CrossRef]
Woolthuis CM, Park CY. Hematopoietic stem/progenitor cell commitment to the megakaryocyte lineage. Blood. 2016; 127(10): 1242–1248. [CrossRef]
Peng YJ, Yu H, Hao X, et al. Luteinizing hormone signaling restricts hematopoietic stem cell expansion during puberty. The EMBO Journal. 2018; 37 (17): e98984. [CrossRef]
Sionov RV, Spokoini R, Shlomit KE, Cohen O, Yefenof E. Mechanisms regulating the susceptibility of hematopoietic malignancies to glucocorticoid induced apoptosis. Adv Cancer. 2008; 101:127–248. [CrossRef]
Pham-Huy L, He H, Pham-Huy C. Free radicals, antioxidants in disease and health. Int J Biomed Sci. 2008; 4(2): 89- 96.
Watanabe MAE, Amarante MK, Conti BJ, Sforcin JM. Cytotoxic constituents of propolis inducing anticancer effects: a review. J Pharm Pharmacol. 2011; 63(11): 1378–1386. [CrossRef]
Sengul F, Vatansev H. Overview of apitherapy products: anti-cancer effects of bee venom used in apitherapy. IJTCMR. 2021; 2(1): 36-48.

Abdel-Salam NA, Ghazy NM, Sallam SM, Radwan MM, Wanas AS, ElSohly MA, El-Demellawy MA, Abdel- Rahman NM, Piacente S, Shenouda ML. Flavonoids of Alcea rosea L. and their immune stimulant, antioxidant and cytotoxic activities on hepatocellular carcinoma HepG-2 cell line. Nat Prod Res. 2018; 32(6): 702-706. [CrossRef]
Akyol E, Kaftano lu O. Colony characteristics and the performance of Caucasian (Apis mellifera caucasica) and Mugla (Apis mellifera anatoliaca) bees and their reciprocal crosses. J Apicult Res. 2001; 40: 3-4.
Gomez-Caravaca AM, Gomez-Romero M, Arraez-Roman D, Segura-Carretero A, Fernandez-Gutierrez A. Advances in the analysis of phenolic compounds in products derived from bees. J Pharmaceut Biomed. 2006; 41: 1220–1234. [CrossRef]
Pinto B, Caciagli F, Riccio E, Reali D, Sarić A, Balog T, Likić S, Scarpato R. Antiestrogenic and antigenotoxic activity of bee pollen from Cystus incanus and Salix alba as evaluated by the yeast estrogen screen and the micronucleus assay in human lymphocytes. Eur J Med Chem. 2010; 45(9): 4122-8. [CrossRef]
Silici S, Güçlü BK. Effect of dietary addition of propolis and caffeic acid on the growth performance, production and hatching performance, egg quality and some biochemical parameters of quail (Coturnix coturnix japonica). J Health Sci. 2010; 19(2): 140-150.
Potkonjak NI, Veselinović DS, Novaković MM, Gorjanović SŽ, Pezo LL, Sužnjević DŽ. Antioxidant activity of propolis extracts from Serbia: a polarographic approach. Food Chem Toxicol. 2012; 50(10): 3614–3618. [CrossRef]
Zahid N, Ali A, Siddiqui Y, Maqbool M. Efficacy of ethanolic extract of propolis in maintaining postharvest quality of dragon fruit during storage. Postharvest Biol Tec 2013; 79: 69–72. [CrossRef]
Dogan H, Silici S, Özcimen AA. Biological effects of propolis on cancer. TURJAF 2020; 8(3): 573-579. [CrossRef]
Bogdanov S. Propolis: composition, health, medicine, a review. Bee Product Science www.bee-hexagon.net; 2016.
Carvalho AA, Finger D, Machado CS, et al. In vivo antitumoural activity and composition of an oil extract of Brazilian propolis. Food Chem 2011; 126(3): 1239–1245. [CrossRef]
Murtaza G, Karim S, Akram MR, Khan SA, Azhar S, Mumtaz A, Bin Asad MH. Caffeic acid phenethyl ester and therapeutic potentials. Biomed Res Int. 2014; 9 pages. [CrossRef]
Orsolic N. A review of propolis antitumour action in vivo and in vitro. JAAS 2010; 2(1): 1-20. [CrossRef]
Russo A, Longo R, Vanella A. Antioxidant activity of propolis: role of caffeic acid phenethyl ester and galangin. Fitoterapia. 2002; 73: 21-29. [CrossRef]
Abubakar MB, Abdullah WZ, Sulaiman SA, Ang BS. Polyphenols as key players for the antileukaemic effects of propolis. Evid-Based Compl Alt. 2014; 1-11. [CrossRef]
Rouibah H, Kebsa W, Lahouel M, Zihlif M, Ahram M, Aburmeleih B, Mustafa E, Al-Ameer HJ. Algerian propolis potentiates doxorubicin mediated anticancer effect against human pancreatic PANC-1 cancer cell line through cell cycle arrest, apoptosis induction and p-glycoprotein inhibition. Anticancer Agents Med Chem. 2018; 18(3): 375-387. [CrossRef]
Aslam MS, Naveed S, Ahmed A, Abbas Z, Gull I, Athar MA. Side effects of chemotherapy in cancer patients and evaluation of patients opinion about starvation based differential chemotherapy. J Cancer Ther. 2014; 5: 817-822. [CrossRef]
Hiçsönmez G. A novel approach to treatment in childhood acute myeloblastic leukemia and myelodysplastic syndrome with high-dose methylprednisolone as a differentiation- and apoptosis-inducing agent of myeloid leukemic cells. Turk J Hematol. 2010; 27(1): 1-7.
Kaymaz BT, Selvi N, Saydam G, Sahin F, Kosova B. Methylprednisolone induces apoptosis by interacting with the JAK/STAT pathway in HL-60 and K-562 leukemic cells. Hematology. 2012; 17(2): 93–99. [CrossRef]
Omay SB, Saydam G, Aydın HH, et al. Potential involvement of calcineurin regulating the state of differentiation and apoptosis of HL-60 cells during methylprednisolone-treatment. Turk J Hematol. 2003; 20(3): 143-151.
Uzunoglu S, Uslu R, Tobu M, Saydam G, Terzioglu E, Buyukkececi F, Omay SB. Augmentation of methylprednisolone-induced differentiation of myeloid leukemia cells by erine: threonine protein phosphatase inhibitors. Leuk Res. 1999; 23(5): 507-512. [CrossRef]
Ozcimen AA, Kart A, Okur H, Tuncer AM, Çetin M. The differentiation effect of 6a-methylprednisolone on HL-60 cells. Mersin Univ Fac Med J 2006; 7: 32-36.
Mishima S, Narita Y, Chikamatsu S, Inoh Y, Ohta S, Yoshida C, Araki Y, Akao Y, Suzuki KM, Nozawa Y. Effects of propolis on cell growth and gene expression in HL-60 cells. J Ethnopharmacol. 2005; 99(1): 5–11. [CrossRef]
Kitamura H, Saito N, Fujimoto J, Nakashima KI, Fujikura D. Brazilian propolis ethanol extract and its component kaempferol induce myeloid-derived suppressor cells from macrophages of mice in vivo and in vitro. BMC Complement Altern Med. 2018; 18(1): 138. [CrossRef]
Kuo HC, Kuo WH, Lee YJ, Wang CJ, Tseng TH. Enhancement of caffeic acid phenethyl ester on all-trans retinoic acid-induced differentiation in human leukemia HL-60 cells. Toxicol Appl Pharmacol. 2006; 216(1): 80-8. [CrossRef]
Doğan H, Özçimen AA, Silici S. Effect of cafeic acid phenethyl ester (CAPE) on cell cycle in human acute myeloid leukemia cells. In Book of Abstracts, MEDICRES 7TH International Multidisciplinary Congress on Good Medical Research Conference; Mersin: Turkey; 2020. October 24 – 31.

Details

Primary Language

English

Subjects

Pharmacology and Pharmaceutical Sciences (Other)

Journal Section

Research Article

Authors

Hamide Doğan ^*
0000-0002-6002-6013
Türkiye

Ahmet Ata Ozcimen
0000-0002-8871-8943
Türkiye

Sibel Silici
Türkiye

Publication Date

June 27, 2025

Submission Date

July 4, 2022

Acceptance Date

October 12, 2022

Published in Issue

Year 2023 Volume: 27 Number: 2

IZ

https://izlik.org/JA69NC24CJ

Cite

RIS / Bibtex

APA

Doğan, H., Ozcimen, A. A., & Silici, S. (2025). Effects of olive oil-based propolis, caffeic acid phenethyl ester, and methylprednisolone on differentiation of human acute myeloid leukemia cells. Journal of Research in Pharmacy, 27(2), 677-686. https://izlik.org/JA69NC24CJ

AMA

1.Doğan H, Ozcimen AA, Silici S. Effects of olive oil-based propolis, caffeic acid phenethyl ester, and methylprednisolone on differentiation of human acute myeloid leukemia cells. J. Res. Pharm. 2025;27(2):677-686. https://izlik.org/JA69NC24CJ

Chicago

Doğan, Hamide, Ahmet Ata Ozcimen, and Sibel Silici. 2025. “Effects of Olive Oil-Based Propolis, Caffeic Acid Phenethyl Ester, and Methylprednisolone on Differentiation of Human Acute Myeloid Leukemia Cells”. Journal of Research in Pharmacy 27 (2): 677-86. https://izlik.org/JA69NC24CJ.

EndNote

Doğan H, Ozcimen AA, Silici S (June 1, 2025) Effects of olive oil-based propolis, caffeic acid phenethyl ester, and methylprednisolone on differentiation of human acute myeloid leukemia cells. Journal of Research in Pharmacy 27 2 677–686.

IEEE

[1]H. Doğan, A. A. Ozcimen, and S. Silici, “Effects of olive oil-based propolis, caffeic acid phenethyl ester, and methylprednisolone on differentiation of human acute myeloid leukemia cells”, J. Res. Pharm., vol. 27, no. 2, pp. 677–686, June 2025, [Online]. Available: https://izlik.org/JA69NC24CJ

ISNAD

Doğan, Hamide - Ozcimen, Ahmet Ata - Silici, Sibel. “Effects of Olive Oil-Based Propolis, Caffeic Acid Phenethyl Ester, and Methylprednisolone on Differentiation of Human Acute Myeloid Leukemia Cells”. Journal of Research in Pharmacy 27/2 (June 1, 2025): 677-686. https://izlik.org/JA69NC24CJ.

JAMA

1.Doğan H, Ozcimen AA, Silici S. Effects of olive oil-based propolis, caffeic acid phenethyl ester, and methylprednisolone on differentiation of human acute myeloid leukemia cells. J. Res. Pharm. 2025;27:677–686.

MLA

Doğan, Hamide, et al. “Effects of Olive Oil-Based Propolis, Caffeic Acid Phenethyl Ester, and Methylprednisolone on Differentiation of Human Acute Myeloid Leukemia Cells”. Journal of Research in Pharmacy, vol. 27, no. 2, June 2025, pp. 677-86, https://izlik.org/JA69NC24CJ.

Vancouver

1.Hamide Doğan, Ahmet Ata Ozcimen, Sibel Silici. Effects of olive oil-based propolis, caffeic acid phenethyl ester, and methylprednisolone on differentiation of human acute myeloid leukemia cells. J. Res. Pharm. [Internet]. 2025 Jun. 1;27(2):677-86. Available from: https://izlik.org/JA69NC24CJ