Hyaluronic Acid-Curcumin Complex Triggers Apoptotic Pathway in Breast Cancer Cells via CD44 Receptors

Mokhberioskouei, Ziba; Biçim, Gökhan; Yılmaz Göler, Ayşe Mine; Yalcin, A. Suha

doi:10.33808/clinexphealthsci.1185564

Hyaluronic Acid-Curcumin Complex Triggers Apoptotic Pathway in Breast Cancer Cells via CD44 Receptors

Ziba MOKHBERİ OSKOUEİ, (Marmara Üniversitesi, Tıp Fakültesi, ve Sağlık Bilimleri Enstitüsü, Tıbbi Biyokimya Anabilim Dalı, İstanbul, Türkiye)

Gökhan BİÇİM, (Marmara Üniversitesi, Tıp Fakültesi, ve Sağlık Bilimleri Enstitüsü, Tıbbi Biyokimya Anabilim Dalı, İstanbul, Türkiye)

Ayse Mine YILMAZ GÖLER, (Marmara Üniversitesi, Tıp Fakültesi, ve Sağlık Bilimleri Enstitüsü, Tıbbi Biyokimya Anabilim Dalı, İstanbul, Türkiye)

A. Süha YALÇIN (Marmara Üniversitesi, Tıp Fakültesi, ve Sağlık Bilimleri Enstitüsü, Tıbbi Biyokimya Anabilim Dalı, İstanbul, Türkiye)

Clinical and Experimental Health Sciences

5 5

Yıl: 2023 Cilt: 13 Sayı: 3 Sayfa Aralığı: 658 - 663 Metin Dili: İngilizce DOI: 10.33808/clinexphealthsci.1185564 İndeks Tarihi: 19-09-2023

Hyaluronic Acid-Curcumin Complex Triggers Apoptotic Pathway in Breast Cancer Cells via CD44 Receptors

Öz:

Objective: Curcumin (CUR) was modified with hyaluronic acid (HA) to increase its water solubility and bioavailability. Our aim was to increase the uptake of CUR into the cells that express CD44 receptors and to compare the cellular effects in two different human breast carcinoma cells, MCF-7 and MDA-MB-231. Methods: Hyaluronic acid-curcumin complex (HA-CUR) was synthesized and characterized. MCF-7 and MDA-MB-231 cells were grown under appropriate conditions and the effect of CUR and HA-CUR on cell viability was determined. Apoptosis levels of cells after treatment with CUR and HA-CUR were also measured. CD44 receptor levels of both cells were compared and then apoptosis levels were measured in MDA-MB-231 cells after saturation of CD 44 receptors with HA. In both cells expression of caspase-9 and PARP was analyzed to confirm apoptosis. Results: In MCF-7 cells, the percentage apoptosis level of the CUR group was slightly lower than the HA-CUR group. In MDA-MB-231 cells, no statistically significant difference was found in the CUR group compared to the control group, but the apoptosis level of the HA-CUR group was higher than the control group. CD44 receptor levels were higher in MDA-MB-231 cells compared to MCF-7 cells. Blocking the CD44 receptors reversed the apoptotic effect of HA-CUR in MDA-MB-231 cells. Both CUR and HA-CUR had apoptotic effects in MCF-7 and MDA-MB-231 cells. Conclusion: Conjugation of CUR with HA, which is specific for CD44 receptors aids, in its entry to target cells making it a powerful agent for targeted cancer therapy.

Anahtar Kelime: Hyaluronic acid Curcumin MCF-7 MDA-MB-231 CD44 receptor

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

[1] Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: Preclinical and clinical studies. Anticancer Res. 2003;23(1/A):363-398.
[2] Kunnumakkara AB, Bordoloi D, Padmavathi G, Monisha J, Roy NK, Prasad S, Aggarwal BB. Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases. Br J Pharmacol. 2017;174(11):1325-1348. DOI:10.1111/bph.13621
[3] Platt VM, Szoka Jr FC. Anticancer therapeutics: Targeting macromolecules and nanocarriers to hyaluronan or CD44, a hyaluronan receptor. Mol Pharm. 2008;5(4):474-486. DOI:10.1021/mp800024g
[4] Kesharwani P, Chadar R, Sheikh A, Rizg WY, Safhi AY. CD44- targeted nanocarrier for cancer therapy. Front Pharmacol. 2021;12 DOI:10.3389/fphar.2021.800481
[5] Byeon Y, Lee J-W, Choi WS, Won JE, Kim GH, Kim MG, Wi TI, Lee JM, Kang TH, Jung ID. CD44-targeting PLGA nanoparticles incorporating paclitaxel and FAK siRNA overcome chemoresistance in epithelial ovarian cancerovercoming chemoresistance by HA-PLGA-NP in ovarian cancer. Cancer Res. 2018;78(21):6247-6256. DOI:10.1158/0008-5472.CAN- 17-3871
[6] Cao A, Ma P, Yang T, Lan Y, Yu S, Liu L, Sun Y, Liu Y. Multifunctionalized micelles facilitate intracellular doxorubicin delivery for reversing multidrug resistance of breast cancer. Mol Pharm. 2019;16(6):2502-2510. DOI:10.1021/acs. molpharmaceut.9b00094
[7] Manju S, Sreenivasan K. Conjugation of curcumin onto hyaluronic acid enhances its aqueous solubility and stability. J Colloid Interface Sci. 2011;359(1):318-325. DOI:10.1016/j. jcis.2011.03.071
[8] Mutlu Altundağ E, Yılmaz AM, Koçtürk S, Taga Y, Yalçın AS. Synergistic induction of apoptosis by quercetin and curcumin in chronic myeloid leukemia (K562) cells . Nutr Cancer. 2018;70(1):97-108. DOI:10.1080/01635.581.2020.1767167
[9] Giordano A and Tommonaro G. Curcumin and cancer. Nutrients 2019;11(10):2376. DOI:10.3390/nu11102376
[10] Hu S, Xu Y, Meng L, Huang L, Sun H. Curcumin inhibits proliferation and promotes apoptosis of breast cancer cells. Exp Ther Med. 2018;16(2):1266-1272. DOI:10.3892/ etm.2018.6345
[11] Diao L, Shen A, Yang Y, Tao J, Hu Y. CD44-targeted hyaluronic acid–curcumin reverses chemotherapeutics resistance by inhibiting P-gp and anti-apoptotic pathways. RSC Adv. 2019;9(70):40873-40882. DOI:10.1039/C9RA08202F
[12] Ji P, Wang L, Chen Y, Wang S, Wu Z, Qi X. Hyaluronic acid hydrophilic surface rehabilitating curcumin nanocrystals for targeted breast cancer treatment with prolonged biodistribution. Biomater Sci. 2020;8(1):462-472. https://doi. org/10.1039/C9BM01605H
[13] Mutlu Altundağ E, Yılmaz AM, Serdar BS, Jannuzzi AT, Koçtürk S, Yalçın AS. Synergistic induction of apoptosis by quercetin and curcumin in chronic myeloid leukemia (K562) cells: II. signal transduction pathways involved. Nutr Cancer. 2021;73(4):703- 712.
[14] Ghosh S, Dutta S, Sarkar A, Kundu M, Sil PC. Targeted delivery of curcumin in breast cancer cells via hyaluronic acid modified mesoporous silica nanoparticle to enhance anticancer efficiency. Colloids and Surfaces B: Biointerfaces. 2021;197:111404.
[15] Yang C, Liu Y, He Y, Du Y, Wang W, Shi X, Gao F. The use of HA oligosaccharide-loaded nanoparticles to breach the endogenous hyaluronan glycocalyx for breast cancer therapy. Biomaterials. 2013;34(28):6829-6838. DOI: 10.1016/j. biomaterials.2013.05.036
[16] Vikram R, Chou WC, Hung S-C, Shen C-Y. Tumorigenic and metastatic role of CD44−/low/CD24−/low cells in luminal breast cancer. Cancers. 2020;12(5):1239.
[17] Toole BP and Slomiany MG. Hyaluronan: A constitutive regulator of chemoresistance and malignancy in cancer cells. Seminars in Cancer Biology. 2008;18(4):244-250. DOI:10.1016/j.semcancer.2008.03.009
[18] Yang C, Cao M, Liu H, He Y, Xu J, Du Y, Liu Y, Wang W, Cui L, Hu J, Gao F. The high and low molecular weight forms of hyaluronan have distinct effects on CD44 clustering. J Biol Chem. 2012;287(51):43094-43107. DOI:10.1074/jbc. M112.349209
[19] Chiu TL, Su CC. Curcumin inhibits proliferation and migration by increasing the Bax to Bcl-2 ratio and decreasing NF-kappaBp65 expression in breast cancer MDA-MB-231 cells. Int J Mol Med. 2009;23(4):469-475. DOI:10.3892/ijmm_00000153
[20] Slomiany MG, Dai L, Bomar PA, Knackstedt TJ, Kranc DA, Tolliver L, Maria BL, Toole BP. Abrogating drug resistance in malignant peripheral nerve sheath tumors by disrupting hyaluronan-CD44 interactions with small hyaluronan oligosaccharides. Cancer Res. 2009;69(12):4992-4998.

APA	Mokhberioskouei Z, Biçim G, Yılmaz Göler A, Yalcin A (2023). Hyaluronic Acid-Curcumin Complex Triggers Apoptotic Pathway in Breast Cancer Cells via CD44 Receptors. , 658 - 663. 10.33808/clinexphealthsci.1185564
Chicago	Mokhberioskouei Ziba,Biçim Gökhan,Yılmaz Göler Ayşe Mine,Yalcin A. Suha Hyaluronic Acid-Curcumin Complex Triggers Apoptotic Pathway in Breast Cancer Cells via CD44 Receptors. (2023): 658 - 663. 10.33808/clinexphealthsci.1185564
MLA	Mokhberioskouei Ziba,Biçim Gökhan,Yılmaz Göler Ayşe Mine,Yalcin A. Suha Hyaluronic Acid-Curcumin Complex Triggers Apoptotic Pathway in Breast Cancer Cells via CD44 Receptors. , 2023, ss.658 - 663. 10.33808/clinexphealthsci.1185564
AMA	Mokhberioskouei Z,Biçim G,Yılmaz Göler A,Yalcin A Hyaluronic Acid-Curcumin Complex Triggers Apoptotic Pathway in Breast Cancer Cells via CD44 Receptors. . 2023; 658 - 663. 10.33808/clinexphealthsci.1185564
Vancouver	Mokhberioskouei Z,Biçim G,Yılmaz Göler A,Yalcin A Hyaluronic Acid-Curcumin Complex Triggers Apoptotic Pathway in Breast Cancer Cells via CD44 Receptors. . 2023; 658 - 663. 10.33808/clinexphealthsci.1185564
IEEE	Mokhberioskouei Z,Biçim G,Yılmaz Göler A,Yalcin A "Hyaluronic Acid-Curcumin Complex Triggers Apoptotic Pathway in Breast Cancer Cells via CD44 Receptors." , ss.658 - 663, 2023. 10.33808/clinexphealthsci.1185564
ISNAD	Mokhberioskouei, Ziba vd. "Hyaluronic Acid-Curcumin Complex Triggers Apoptotic Pathway in Breast Cancer Cells via CD44 Receptors". (2023), 658-663. https://doi.org/10.33808/clinexphealthsci.1185564

APA	Mokhberioskouei Z, Biçim G, Yılmaz Göler A, Yalcin A (2023). Hyaluronic Acid-Curcumin Complex Triggers Apoptotic Pathway in Breast Cancer Cells via CD44 Receptors. Clinical and Experimental Health Sciences, 13(3), 658 - 663. 10.33808/clinexphealthsci.1185564
Chicago	Mokhberioskouei Ziba,Biçim Gökhan,Yılmaz Göler Ayşe Mine,Yalcin A. Suha Hyaluronic Acid-Curcumin Complex Triggers Apoptotic Pathway in Breast Cancer Cells via CD44 Receptors. Clinical and Experimental Health Sciences 13, no.3 (2023): 658 - 663. 10.33808/clinexphealthsci.1185564
MLA	Mokhberioskouei Ziba,Biçim Gökhan,Yılmaz Göler Ayşe Mine,Yalcin A. Suha Hyaluronic Acid-Curcumin Complex Triggers Apoptotic Pathway in Breast Cancer Cells via CD44 Receptors. Clinical and Experimental Health Sciences, vol.13, no.3, 2023, ss.658 - 663. 10.33808/clinexphealthsci.1185564
AMA	Mokhberioskouei Z,Biçim G,Yılmaz Göler A,Yalcin A Hyaluronic Acid-Curcumin Complex Triggers Apoptotic Pathway in Breast Cancer Cells via CD44 Receptors. Clinical and Experimental Health Sciences. 2023; 13(3): 658 - 663. 10.33808/clinexphealthsci.1185564
Vancouver	Mokhberioskouei Z,Biçim G,Yılmaz Göler A,Yalcin A Hyaluronic Acid-Curcumin Complex Triggers Apoptotic Pathway in Breast Cancer Cells via CD44 Receptors. Clinical and Experimental Health Sciences. 2023; 13(3): 658 - 663. 10.33808/clinexphealthsci.1185564
IEEE	Mokhberioskouei Z,Biçim G,Yılmaz Göler A,Yalcin A "Hyaluronic Acid-Curcumin Complex Triggers Apoptotic Pathway in Breast Cancer Cells via CD44 Receptors." Clinical and Experimental Health Sciences, 13, ss.658 - 663, 2023. 10.33808/clinexphealthsci.1185564
ISNAD	Mokhberioskouei, Ziba vd. "Hyaluronic Acid-Curcumin Complex Triggers Apoptotic Pathway in Breast Cancer Cells via CD44 Receptors". Clinical and Experimental Health Sciences 13/3 (2023), 658-663. https://doi.org/10.33808/clinexphealthsci.1185564