Effects of Apigenin and Apigenin- Loaded Nanogel on Induction of Apoptosis in Human Chronic Myeloid Leukemia Cells

  • Mehrdad Hashemi
  • Nooshin Samadian
Keywords: Apigenin, Nanogel, Chitosan, Flavonoid


Background: Diet plays an important role in cancer prevention. Apigenin, a flavonoid with thechemical formula C15H10O5, is abundantly present in vegetables. Vegetarian foods containing flavonoids are rich sources of bioactive compounds. Flavonoids have been utilized in herbal treatment. Nanogels are drug delivery systems based on polymers and are used in tissue engineering and for drug delivery. This study was conducted to compare the effects of apigenin and a nanodrug on the viability of the K562 cell line of chronic myeloid leukemia at different durations under laboratory conditions. Materials and Methods: Chitosan was first dissolved in 1% acetic acid, and  ethylene dichloride EDC and NHS were added to the solution. Then, the nanodrug was prepared by loading apigenin into stearate–chitosan nanogel (scs nanogel), and its physical and morphological characteristics were evaluated by TEM, DLS, and FTIR. Trypan blue staining, MTT assay, and flow cytometry were used to analyze the effects of various concentrations of apigenin and apigenin-loaded chitosan–stearate nanogel (APG–SCS) at 24, 48, and 72 h after they were applied to the K562 cell line. Results: The diameter of the nanodrug particles was measured using DLS and confirmed by TEM. The K562 cells treated with APG–SCS and with apigenin exhibited significant differences compared with the control (P < 0.05). Apoptosis was detected by flow cytometry. Conclusion: This study showed that the toxic effects of apigenin and the nanodrug improved with increasing concentrations and exposure durations compared to those in the control.The toxic effect of apigenin loaded into the stearate-chitosan nanogel was greater than apigenin, and the toxic effects of both materials were greater compared to the control under laboratory conditions.[GMJ.2018;7:e1008]


Bhamidipati PK, Kantarjian H, Cortes J, Cornelison AM, Jabbour E. Management of imatinib-resistant patients with chronic myeloid leukemia. Ther Adv Hematol. 2013;4(2):103-17.

A Mahbub A, Maitre C, L Haywood-Small S, J McDougall G, A Cross N, Jordan-Mahy N. Differential effects of polyphenols on proliferation and apoptosis in human myeloid and lymphoid leukemia cell lines. Anticancer Agents Med Chem. 2013;13(10):1601-13.

Solmaz S, Adan Gokbulut A, Cincin B, Ozdogu H, Boga C, Cakmakoglu B, et al. Therapeutic potential of apigenin, a plant flavonoid for imatinib-sensitive and resistant chronic myeloid leukemia cells. Nutr Cancer. 2014;66(4):599-12.

Mahbub A, Le Maitre C, Haywood-Small S, Cross N, Jordan-Mahy N. Polyphenols act synergistically with doxorubicin and etoposide in leukaemia cell lines. Cell Death Discov. 2015;1(43):15043-55.

Qinghong S, Shen G, Lina S, Yueming Z, Xiaoou L, Jianlin W, et al. Comparative proteomics analysis of differential proteins in respond to doxorubicin resistance in myelogenous leukemia cell lines. Proteome Sci. 2015;13(1):1-12.

Cai H, Qin X, Yang C. Dehydrocostus Lactone Suppresses Proliferation of Human Chronic Myeloid Leukemia Cells Through Bcr/Abl‐JAK/STAT Signaling Pathways. J Cell Biochem. 2017;118(10):3381-90.

Heydarirad G, Sadeghi SM, Khameneh SM, Khodadoost M, Kamalinejad M, Jafari S, et al. Effects of Natural Substances on Healing of Long Bone Fractures: A Narrative Review of Traditional Persian Medicine. GMJ. 2016;5(4):165-72.

Azimi M, Zahedi MJ, Mehrabani M, Tajadini H, Zolala F, Baneshi MR, et al. Effects of Iranian Traditional Medicine Remedies (Apium Graveolence and Trachyspermum Copticum) on Modifying the Quality of Life in Patients with Functional Dyspepsia: A Double-Blind Randomized Clinical Trial. GMJ. 2017;6(2):102-9.

Gurung RB, Kim EH, Oh TJ, Sohng JK. Enzymatic synthesis of apigenin glucosides by glucosyltransferase (YjiC) from Bacillus licheniformis DSM 13. Mol Cells. 2013;36(4):355-61.

Tong X, C Pelling J. Targeting the PI3K/Akt/mTOR axis by apigenin for cancer prevention. Anticancer Agents Med Chem. 2013;13(7):971-8.

Maggioni D, Garavello W, Rigolio R, Pignataro L, Gaini R, Nicolini G. Apigenin impairs oral squamous cell carcinoma growth in vitro inducing cell cycle arrest and apoptosis. Int J Oncol. 2013;43(5):1675-82.

Xu Y, Xin Y, Diao Y, Lu C, Fu J, Luo L, et al. Synergistic effects of apigenin and paclitaxel on apoptosis of cancer cells. PLoS One. 2011;6(12):29169-81.

Salmani JM, Zhang XP, Jacob JA, BaoAn CH. Apigenin's anticancer properties and molecular mechanisms of action Recent advances and future prospectives. Chin J Nat Med. 2017;15(5):321-9.

Hashemi M, Long MN, Entezari M, Nafisi S, Nowroozii H. Anti-mutagenic and pro-apoptotic effects of apigenin on human chronic lymphocytic leukemia cells. Acta Med Iran. 2010;48(5):283-9.

Pashaei R. Features of Apigenin, Luteolin, Hesperetin and Naringenin in Crop and Body. Nutr Diet. 2016;5(5):300-4.

Perrott KM, Wiley CD, Desprez PY, Campisi J. Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells. Geroscience. 2017; 39(2):161-73.

Chunhua L, Donglan L, Xiuqiong F, Lihua Z, Qin F, Yawei L, et al. Apigenin up-regulates transgelin and inhibits invasion and migration of colorectal cancer through decreased phosphorylation of AKT. J Nutr Biochem. 2013;24(10):1766-75.

Zhang H, Zhai Y, Wang J, Zhai G. New progress and prospects: The application of nanogel in drug delivery. Sci Eng C Mater. 2016;60(11):560-8.

Sao Pedro A, Cabral-Albuquerque E, Ferreira D, Sarmento B. Chitosan An option for development of essential oil delivery systems for oral cavity care. Carbohydr Polym. 2009; 76(4):501-8.

Atabi F, Gargari SL, Hashemi M, Yaghmaei P. Doxorubicin Loaded DNA Aptamer Linked Myristilated Chitosan Nanogel for Targeted Drug Delivery to Prostate Cancer. Iran J Pharm Res. 2017;16(1):35-49.

Banerjee B, Chakraborty S, Ghosh D, Raha S, Sen PC, Jana K. Benzo (a) pyrene induced p53 mediated male germ cell apoptosis: Synergistic protective effects of curcumin and resveratrol. Front Pharmacol. 2016;7(2):245-65.

Lee KW, Bode AM, Dong Z. Molecular Targets Of Phytochemicals for Cancer Prevention. Nat Rev Cancer. 2011;11(3):211-8.

Mehranfar S, Zeinali S, Hosseini R, Mohammadian M, Akbarzadeh A, Feizi AH. History of Leukemia: Diagnosis and Treatment from Beginning to Now. GMJ. 2017;6(1):12-22.

Pawlikowska-Pawlęga B, Misiak LE, Zarzyka B, Paduch R, Gawron A, Gruszecki WI. FTIR 1 H NMR and EPR spectroscopy studies on the interaction of flavone apigenin with dipalmitoylphosphatidylcholine liposomes. Biochim Biophys Acta. 2013;1828(2):518-27

Xie YT, Du YZ, Yuan H, Hu FQ. Brain-targeting study of stearic acid-grafted chitosan micelle drug-delivery system. Int J Nanomedicine. 2012;7(1):3235-44.

Wang L, Kuang L, Hitron JA, Son YO, Wang X, Budhraja A, et al. Apigenin suppresses migration and invasion of transformed cells through down-regulation of CXC chemokine receptor 4 expression. Toxicol Appl Pharmacol. 2013;272(1):108-16.

Bokulic A, Garaj-Vrhovac V, Brajsa K, Duric K, Glojnaric I, Situm K. The effect of apigenin on cyclophosphamide and doxorubicin genotoxicity in vitro and in vivo. J Environ Sci Health A 2011;46(5):526-33.

Das S, Das J, Samadder A, Paul A, Khuda-Bukhsh AR. Efficacy of PLGA-loaded apigenin nanoparticles in Benzo [a] pyrene and ultraviolet-B induced skin cancer of mice: Mitochondria mediated apoptotic signalling cascades. Food Chem Toxicol. 2013;62(10):670-80.

Arsic I, Tadic V, Vlaovic D, Homsek I, Vesic S, Isailovic G, et al. Preparation of novel apigenin‐enriched, liposomal and non‐liposomal, antiinflammatory topical formulations as substitutes for corticosteroid therapy. Phytother Res. 2011;25(2):228-33.

Zhai Y, Guo S, Liu C, Yang C, Dou J, Li L, et al. Preparation and in vitro evaluation of apigenin-loaded polymeric micelles. Colloids Surf A Physicochem Eng Asp. 2013;429(3):24-30.

Liu J, Cao XC, Xiao Q, Quan MF. Apigenin inhibits HeLa sphere-forming cells through inactivation of casein kinase 2α. Mol Med Rep. 2015;11(1):665-9.

Ren HY, Tang XW. Antiproliferaiton and chemo-sensitization effects of apigenin on human lung cancer cells. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2011;40(5):508-14.

Zhao M, Ma J, Zhu HY, Zhang XH, Du ZY, Xu YJ, et al. Apigenin inhibits proliferation and induces apoptosis in human multiple myeloma cells through targeting the trinity of CK2, Cdc37 and Hsp90. Mol Cancer. 2011;10(1):104-18.

Tsalkidou EG, Tsaroucha AK, Chatzaki E, Lambropoulou M, Papachristou F, Trypsianis G, et al. The effects of apigenin on the expression of Fas/FasL apoptotic pathway in warm liver ischemia-reperfusion injury in rats. Biomed Res Int. 2014; 2014(10):216-23.

Ruela-de-Sousa RR, Fuhler GM, Blom N, Ferreira CV, Aoyama H, Peppelenbosch MP. Cytotoxicity of apigenin on leukemia cell lines implications for prevention and therapy. Cell Death Dis. 2010;1(1):507-19.

How to Cite
Hashemi, M., & Samadian, N. (2018). Effects of Apigenin and Apigenin- Loaded Nanogel on Induction of Apoptosis in Human Chronic Myeloid Leukemia Cells. Galen Medical Journal, 7, e1008. https://doi.org/10.22086/gmj.v0i0.1008
Original Article