Phloroglucinol targets prostate cancer cells by inducing cytotoxic and apoptotic responses

Filiz Bakar Ateş; Zeynep Rümeysa Karabulut

doi:10.12991/jrespharm.1798435

Phloroglucinol targets prostate cancer cells by inducing cytotoxic and apoptotic responses

Abstract

The importance of naturally derived products in cancer treatment is well known. In recent years, studies on the activities of compounds isolated from such products against various cancer cells have gained momentum. Phlorotannins are oligomeric compounds found in brown algae, and phloroglucinol (1,3,4-trihydroxybenzene) is a phlorotannin isolated from Ecklonia species. Research has shown that phloroglucinol may have antithrombotic and profibrinolytic activities, as well as potential effectiveness in cancer. This study aimed to evaluate the anticancer activity of phloroglucinol on human prostate cancer cells. In this context, androgen-independent PC3 human prostate cancer cells were used, and the cytotoxic effect of phloroglucinol on these cells was evaluated using the MTT assay. Annexin V binding analysis was performed to assess the apoptotic effect. Phloroglucinol significantly reduced cell viability at concentrations of 1 mM and above at 24 and 48 hours and inhibited the cell cycle in the G2/M phase. Additionally, it was found that the compound significantly increased apoptotic cell population % in PC3 human prostate cancer cells at the IC50 concentration, inducing apoptosis. Phloroglucinol is a naturally derived compound, and there is limited research in the literature regarding its effectiveness in cancer. This study represents the first evaluation of the apoptotic activity of this compound in prostate cancer cells. Therefore, the findings of this study are crucial for guiding further research on this compound.

Keywords

References

Rawla P. Epidemiology of prostate cancer. World J Oncol. 2019; 10(2): 63-89. https://doi.org/10.14740/wjon1191 Yamada Y, Beltran H. The treatment landscape of metastatic prostate cancer. Cancer Lett. 2021; 519: 20-29. https://doi.org/10.1016/j.canlet.2021.06.010
Zerbib M, Zelefsky MJ, Higano CS, Carroll PR. Conventional treatments of localized prostate cancer. Urology. 2008; 72(6 Suppl): 25-35. https://doi.org/10.1016/j.urology.2008.10.005
Asma ST, Acaroz U, Imre K, Morar A, Shah SRA, Hussain SZ, Arslan-Acaroz D, Demirbas H, Hajrulai-Musliu Z, Istanbullugil FR, Soleimanzadeh A, Morozov D, Zhu K, Herman V, Ayad A, Athanassiou C, Ince S. Natural products/bioactive compounds as a source of anticancer drugs. Cancers (Basel). 2022; 14(24): 6203. https://doi.org/10.3390/cancers14246203
Yoon JY, Choi H, Jun HS. The Effect of phloroglucinol, a component of Ecklonia cava extract, on hepatic glucose production. Mar Drugs. 2017; 15(4): 106. https://doi.org/10.3390/md15040106
Bridi H, Meirelles GC, von Poser GL. Structural diversity and biological activities of phloroglucinol derivatives from Hypericum species. Phytochemistry. 2018; 155: 203-232. https://doi.org/10.1016/j.phytochem.2018.08.002
Rocha L, Marston A, Potterat O, Kaplan MA, Stoeckli-Evans H, Hostettmann K. Antibacterial phloroglucinols and flavonoids from Hypericum brasiliense. Phytochemistry. 1995; 40(5): 1447-1452. https://doi.org/10.1016/0031- 9422(95)00507-4
Kim J, Won Choi J, Jeong Kim H, Kim B, Kim Y, Hwejin Lee E, Kim R, Kim J, Park J, Jeong Y, Park JH, Duk Park K. Phloroglucinol derivatives exert anti-ınflammatory effects and attenuate cognitive ımpairment in LPS-ınduced mouse model. ChemMedChem. 2024; 19(17): e202400056. https://doi.org/10.1002/cmdc.202400056
Quéguineur B, Goya L, Ramos S, Martín MA, Mateos R, Bravo L. Phloroglucinol: antioxidant properties and effects on cellular oxidative markers in human HepG2 cell line. Food Chem Toxicol. 2012; 50(8): 2886-2893. https://doi.org/10.1016/j.fct.2012.05.026

Kang MH, Kim IH, Nam TJ. Phloroglucinol induces apoptosis via apoptotic signaling pathways in HT-29 colon cancer cells. Oncol Rep. 2014; 32(4): 1341-1346. https://doi.org/10.3892/or.2014.3355
El Gaafary M, Saber FR, Mahrous EA, Ashour RM, Okba MM, Jin L, Lang SJ, Schmiech M, Simmet T, Syrovets T. The phloroglucinol calcitrinone A, a novel mitochondria-targeting agent, induces cell death in breast cancer cells. Food Chem Toxicol. 2022; 162: 112896. https://doi.org/10.1016/j.fct.2022.112896
Kwon YH, Jung SY, Kim JW, Lee SH, Lee JH, Lee BY, Kwon SM. Phloroglucinol inhibits the bioactivities of endothelial progenitor cells and suppresses tumor angiogenesis in LLC-tumor-bearing mice. PLoS One. 2012; 7(4): e33618. https://doi.org/10.1371/journal.pone.0033618
Bhosale PB, Ha SE, Vetrivel P, Kim HH, Kim SM, Kim GS. Functions of polyphenols and its anticancer properties in biomedical research: A narrative review. Transl Cancer Res. 2020; 9(12): 7619-7631. https://doi.org/10.21037/tcr- 20-2359
Kopustinskiene DM, Jakstas V, Savickas A, Bernatoniene J. Flavonoids as Anticancer Agents. Nutrients. 2020; 12(2): 457. https://doi.org/10.3390/nu12020457
Dhyani P, Quispe C, Sharma E, Bahukhandi A, Sati P, Attri DC, Szopa A, Sharifi-Rad J, Docea AO, Mardare I, Calina D, Cho WC. Anticancer potential of alkaloids: A key emphasis to colchicine, vinblastine, vincristine, vindesine, vinorelbine and vincamine. Cancer Cell Int. 2022; 22(1): 206. https://doi.org/10.1186/s12935-022-02624- 9
Zhang S, Ye T, Liu Y, Hou G, Wang Q, Zhao F, Li F, Meng Q. Research advances in clinical applications, anticancer mechanism, total chemical synthesis, semi-synthesis and biosynthesis of paclitaxel. Molecules. 2023; 28(22): 7517. https://doi.org/10.3390/molecules28227517
Liu Z, Yuan Y, Wang N, Yu P, Teng Y. Drug combinations of camptothecin derivatives promote the antitumor properties. Eur J Med Chem. 2024; 279: 116872. https://doi.org/10.1016/j.ejmech.2024.116872
Silk N, Reich J, Sinha R, Chawla S, Geary K, Zhang D. The Effects of resveratrol on prostate cancer through targeting the tumor microenvironment. J Xenobiot. 2021; 11(1): 16-32. https://doi.org/10.3390/jox11010002
Albrecht DS, Clubbs EA, Ferruzzi M, Bomser JA. Epigallocatechin-3-gallate (EGCG) inhibits PC-3 prostate cancer cell proliferation via MEK-independent ERK1/2 activation. Chem Biol Interact. 2008; 171(1): 89-95. https://doi.org/10.1016/j.cbi.2007.09.001
Mukherjee S, Siddiqui MA, Dayal S, Ayoub YZ, Malathi K. Epigallocatechin-3-gallate suppresses proinflammatory cytokines and chemokines induced by Toll-like receptor 9 agonists in prostate cancer cells. J Inflamm Res. 2014; 7: 89-101. https://doi.org/10.2147/JIR.S61365
Pourali M, Yaghoobi MM, Salehi Sormaghi MH. Cytotoxic, anti-proliferative and apoptotic effects of tribulus terrestris L. fruit extract on human prostate cancer Lncap and colon cancer HT-29 cell lines. Jundishapur J Nat Pharm Prod. 2016; 12(2): e33561. https://doi.org/10.5812/jjnpp.33561
El Gaafary M, Saber FR, Mahrous EA, Ashour RM, Okba MM, Jin L, Lang SJ, Schmiech M, Simmet T, Syrovets T. The phloroglucinol calcitrinone A, a novel mitochondria-targeting agent, induces cell death in breast cancer cells. Food Chem Toxicol. 2022; 162: 112896. https://doi.org/10.1016/j.fct.2022.112896
Le DH, Nishimura K, Takenaka Y, Mizushina Y, Tanahashi T. Polyprenylated Benzoylphloroglucinols with DNA Polymerase Inhibitory Activity from the Fruits of Garcinia schomburgkiana. J Nat Prod. 2016; 79(7): 1798-807. https://doi.org/10.1021/acs.jnatprod.6b00255
Zhang S, Xiao X, Yi Y, Wang X, Zhu L, Shen Y, Lin D, Wu C. Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets. Sig Transduct Target Ther. 2024; 9: 149. https://doi.org/10.1038/s41392- 024-01848-7
Bailon-Moscoso N, Cevallos-Solorzano G, Romero-Benavides JC, Orellana MI. Natural compounds as modulators of cell cycle arrest: Application for anticancer chemotherapies. Curr Genomics. 2017; 18(2): 106-131. https://doi.org/10.2174/1389202917666160808125645
Sun Y, Mu F, Li C, Wang W, Luo M, Fu Y, Zu Y. Aspidin BB, a phloroglucinol derivative, induces cell cycle arrest and apoptosis in human ovarian HO-8910 cells. Chem Biol Interact. 2013; 204(2): 88-97. https://doi.org/10.1016/j.cbi.2013.04.008.
Mustafa M, Ahmad R, Tantry IQ, Ahmad W, Siddiqui S, Alam M, Abbas K, Moinuddin, Hassan MI, Habib S, Islam S. Apoptosis: A comprehensive overview of signaling pathways, morphological changes, and physiological significance and therapeutic ımplications. Cells. 2024; 13(22): 1838. https://doi.org/10.3390/cells13221838
Naeem A, Hu P, Yang M, Zhang J, Liu Y, Zhu W, Zheng Q. Natural products as anticancer agents: Current status and future perspectives. Molecules. 2022; 27: 8367. https://doi.org/10.3390/molecules27238367
Pham TA, Shair Mohammad I, Vu VT, Hu XL, Birendra C, Ulah A, Guo C, Lü XY, Ye WC, Wang H. Phloroglucinol derivatives from the fruits of Eucalyptus globulus and their cytotoxic activities. Chem Biodivers. 2018; 15(6): e1800052. https://doi.org/10.1002/cbdv.201800052
Lu DY, Chang CS, Yeh WL, Tang CH, Cheung CW, Leung YM, Liu JF, Wong KL. The novel phloroglucinol derivative BFP induces apoptosis of glioma cancer through reactive oxygen species and endoplasmic reticulum stress pathways. Phytomedicine. 2012; 19(12): 1093-1100. https://doi.org/10.1016/j.phymed.2012.06.010
Zhang Y, Luo M, Zu Y, Fu Y, Gu C, Wang W, Yao L, Efferth T. Dryofragin, a phloroglucinol derivative, induces apoptosis in human breast cancer MCF-7 cells through ROS-mediated mitochondrial pathway. Chem Biol Interact. 2012; 199(2): 129-136. https://doi.org/10.1016/j.cbi.2012.06.007
Kim RK, Uddin N, Hyun JW, Kim C, Suh Y, Lee SJ. Novel anticancer activity of phloroglucinol against breast cancer stem-like cells. Toxicol Appl Pharmacol. 2015; 286(3): 143-150. https://doi.org/10.1016/j.taap.2015.03.026.
Muthu S, Lakshmikanthan M, Edward-Sam E, Subramanian M, Govindan L, Patcha ABM, Krishnan K, Duraisamy N, Jeyaperumal S, Aziz AT. Encapsulation of Phloroglucinol from Rosenvingea intricata macroalgae with zinc oxide nanoparticles against A549 Lung Cancer Cells. Pharmaceutics. 2024; 16(10): 1300. https://doi.org/10.3390/pharmaceutics16101300.

Details

Primary Language

English

Subjects

Pharmaceutical Biochemistry

Journal Section

Research Article

Authors

Filiz Bakar Ateş ^*
0000-0003-2809-8946
Türkiye

Zeynep Rümeysa Karabulut
0009-0002-8178-120X
Türkiye

Publication Date

November 2, 2025

Submission Date

April 5, 2025

Acceptance Date

May 3, 2025

Published in Issue

Year 2025 Volume: 29 Number: 6

DOI

https://doi.org/10.12991/jrespharm.1798435

IZ

https://izlik.org/JA47UE43PA

Cite

RIS / Bibtex

APA

Bakar Ateş, F., & Karabulut, Z. R. (2025). Phloroglucinol targets prostate cancer cells by inducing cytotoxic and apoptotic responses. Journal of Research in Pharmacy, 29(6), 2625-2632. https://doi.org/10.12991/jrespharm.1798435

AMA

1.Bakar Ateş F, Karabulut ZR. Phloroglucinol targets prostate cancer cells by inducing cytotoxic and apoptotic responses. J. Res. Pharm. 2025;29(6):2625-2632. doi:10.12991/jrespharm.1798435

Chicago

Bakar Ateş, Filiz, and Zeynep Rümeysa Karabulut. 2025. “Phloroglucinol Targets Prostate Cancer Cells by Inducing Cytotoxic and Apoptotic Responses”. Journal of Research in Pharmacy 29 (6): 2625-32. https://doi.org/10.12991/jrespharm.1798435.

EndNote

Bakar Ateş F, Karabulut ZR (November 1, 2025) Phloroglucinol targets prostate cancer cells by inducing cytotoxic and apoptotic responses. Journal of Research in Pharmacy 29 6 2625–2632.

IEEE

[1]F. Bakar Ateş and Z. R. Karabulut, “Phloroglucinol targets prostate cancer cells by inducing cytotoxic and apoptotic responses”, J. Res. Pharm., vol. 29, no. 6, pp. 2625–2632, Nov. 2025, doi: 10.12991/jrespharm.1798435.

ISNAD

Bakar Ateş, Filiz - Karabulut, Zeynep Rümeysa. “Phloroglucinol Targets Prostate Cancer Cells by Inducing Cytotoxic and Apoptotic Responses”. Journal of Research in Pharmacy 29/6 (November 1, 2025): 2625-2632. https://doi.org/10.12991/jrespharm.1798435.

JAMA

1.Bakar Ateş F, Karabulut ZR. Phloroglucinol targets prostate cancer cells by inducing cytotoxic and apoptotic responses. J. Res. Pharm. 2025;29:2625–2632.

MLA

Bakar Ateş, Filiz, and Zeynep Rümeysa Karabulut. “Phloroglucinol Targets Prostate Cancer Cells by Inducing Cytotoxic and Apoptotic Responses”. Journal of Research in Pharmacy, vol. 29, no. 6, Nov. 2025, pp. 2625-32, doi:10.12991/jrespharm.1798435.

Vancouver

1.Filiz Bakar Ateş, Zeynep Rümeysa Karabulut. Phloroglucinol targets prostate cancer cells by inducing cytotoxic and apoptotic responses. J. Res. Pharm. 2025 Nov. 1;29(6):2625-32. doi:10.12991/jrespharm.1798435