Anti‐proliferative effects of pentagamaboronon‐0‐sorbitol on HER2‐overexpressing breast cancer cells

https://doi.org/10.22146/ijbiotech.67549

Lailatul Qodria(1), Rohmad Yudi Utomo(2), Adam Hermawan(3), Edy Meiyanto(4*)

(1) Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Jl. Sekip Utara, Yogyakarta 55281, Indonesia
(2) Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Jl. Sekip Utara, Yogyakarta 55281, Indonesia; Medicinal Chemistry Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Jl. Sekip Utara, Yogyakarta 55281, Indonesia
(3) Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Jl. Sekip Utara, Yogyakarta 55281, Indonesia; Macromolecular Engineering Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Jl. Sekip Utara, Yogyakarta 55281, Indonesia
(4) Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Jl. Sekip Utara, Yogyakarta 55281, Indonesia; Macromolecular Engineering Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Jl. Sekip Utara, Yogyakarta 55281, Indonesia
(*) Corresponding Author

Abstract


HER2‐positive breast cancer is an aggressive form of the disease that is associated with poor prognosis and chemo‐resistance. As such, investigation continues into the development of a new HER2‐targeted drug for breast cancer. This study investigated the anti‐proliferative activities of pentagamaboronon‐0‐sorbitol (PGB‐0‐So) in HER2‐overexpressing breast cancer (MCF‐7/HER2) cells. The cytotoxicity of PGB‐0‐So was assessed via MTT assay. Flow cytometry with propidium iodide and annexin‐V‐FITC staining was conducted to investigate the mechanism of PGB‐0‐So in inhibiting the proliferation of MCF‐7/HER2 cells. Finally, FACS analysis with 2′,7′–dichlorofluorescin diacetate staining was performed to examine intracellular ROS production. PGB‐0‐So exerted cytotoxicity towards MCF‐7/HER2 breast cancer cells with an IC50 value of 36 μM. PGB‐0‐So induced S‐phase arrest and apoptosis in MCF‐7/HER2 cells. Moreover, PGB‐0‐So could increase intracellular ROS production in MCF‐7/HER2 cells. PGB‐0‐So exerted anti‐proliferative activity towards MCF‐7/HER2 cells. This compound may be developed as a chemotherapeutic agent against HER2‐overexpressing breast cancer.


Keywords


anti‐proliferative; breast cancer; HER2; PGB‐0‐So

Full Text:

PDF


References

Chien MH, Yang WE, Yang YC, Ku CC, Lee WJ, Tsai MY, Lin CW, Yang SF. 2020. Dual targeting of the p38 MAPKHO1 axis and cIAP1/XIAP by demethoxycurcumin triggers caspasemediated apoptotic cell death in oral squamous cell carcinoma cells. Cancers 12(3):1–19. doi:10.3390/cancers12030703.

Choudhuri T, Pal S, Agwarwal ML, Das T, Sa G. 2002. Curcumin induces apoptosis in human breast cancer cells through p53­dependent Bax induction. FEBS Letters 512(1­3):334–340. doi:10.1016/S0014­ 5793(02)02292­5.

De Mattos­Arruda L, Cortes J. 2013. Use of pertuzumab for the treatment of HER2­positive metastatic breast cancer. Adv. Ther. 30(7):645–658. doi:10.1007/s12325­013­0043­2.

Hermawan A, Susidarti RA, Ramadani RD, Qodria L, Utomo RY, Ishimura M, Hattori Y, Ohta Y, Kirihata M, Meiyanto E. 2019. Cellular uptake evaluation of pentagamaboronon­0 (PGB­0) for boron neutron capture therapy (BNCT) against breast cancer cells. Invest. New Drugs 37(6):1292–1299. doi:10.1007/s10637­019­00765­9.

Holmström KM, Finkel T. 2014. Cellular mechanisms and physiological consequences of redox­dependent signalling. Nat. Rev. Mol. Cell Biol. 15(6):411–421. doi:10.1038/nrm3801.

Javvadi P, Segan AT, Tuttle SW, Koumenis C. 2008. The chemopreventive agent curcumin is a potent radiosensitizer of human cervical tumor cells via increased reactive oxygen species production and overactivation of the mitogen­activated protein kinase pathway. Mol. Pharmacol. 73(5):1491–1501. doi:10.1124/mol.107.043554.

Junttila TT, Li G, Parsons K, Phillips GL, Sliwkowski MX. 2011. Trastuzumab­DM1 (T­DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer. Breast Cancer Res. Treat. 128(2):347–356. doi:10.1007/s10549­010­1090­x.

Kusumastuti R, Utomo RY, Khumaira A, Putri H, Jenie RI, Meiyanto E. 2019. Pentagamaboronon­0 increased cytotoxicity of and inhibited metastasis induction by doxorubicin in breast cancer cells. J. Appl. Pharm. Sci. 9(6):043–051. doi:10.7324/JAPS.2019.90606.

Larasati YA, Yoneda­Kato N, Nakamae I, Yokoyama T, Meiyanto E, Kato JY. 2018. Curcumin targets multiple enzymes involved in the ROS metabolic pathway to suppress tumor cell growth. Sci. Rep. 8(1):1–13. doi:10.1038/s41598­018­20179­6.

Lee DS, Lee MK, Kim JH. 2009. Curcumin induces cell cycle arrest and apoptosis in human osteosarcoma (HOS) cells. Anticancer Res. 29(12):5039–5044.

Liu TY, Tan ZJ, Jiang L, Gu JF, Wu XS, Cao Y, Li ML, Wu KJ, Liu YB. 2013. Curcumin induces apoptosis in gallbladder carcinoma cell line GBC­SD cells. Cancer Cell Int. 13(1):1–9. doi:10.1186/1475­2867­13­64.

Luque­-Cabal M, García­Teijido P, Fernández­Pérez Y, Sánchez­Lorenzo L, Palacio­Vázquez I. 2016. Mechanisms behind the resistance to trastuzumab in HER2­amplified breast cancer and strategies to overcome It. Clin. Med. Insights: Oncol. 10:21–30. doi:10.4137/CMO.S34537.

Mendes D, Alves C, Afonso N, Cardoso F, Passos­Coelho JL, Costa L, Andrade S, Batel­Marques F. 2015. The benefit of HER2­targeted therapies on overall survival of patients with metastatic HER2­positive breast cancer ­ a systematic review. Breast Cancer Res. 17(1):1– 14. doi:10.1186/s13058­015­0648­2.

Nguyen KCT, Muthiah M, Islam MA, Kalash RS, Cho CS, Park H, Lee IK, Kim HJ, Park IK, Cho KA. 2014. Selective transfection with osmotically active sorbitol modified PEI nanoparticles for enhanced anti­cancer gene therapy. Colloids Surf., B 119:126– 136. doi:10.1016/j.colsurfb.2014.05.003.

Panieri E, Santoro MM. 2016. Ros homeostasis and metabolism: A dangerous liason in cancer cells. Cell Death Dis. 7(6):e2253–12. doi:10.1038/cddis.2016.105.

Qodria L, Hairunisa I, Utomo RY, Hermawan A, Meiyanto E. 2018. Anti­metastatic Activity of Curcumin Analog Pentagamaboronon­0­Sorbitol Against HER2­overexpressed MCF­7 Breast Cancer Cells. Indones. J. Cancer Chemoprevention 9(3):118. doi:10.14499/indonesianjcanchemoprev9iss3pp118­ 125.

Ramadani RD, Utomo RY, Hermawan A, Meiyanto E. 2018. Curcumin analog pentagamaboronon­ 0­sorbitol inhibits cell migration activity of triple negative breast cancer cell line. Indones. J. Cancer Chemoprevention 9(3):126. doi:10.14499/indonesianjcanchemoprev9iss3pp126­-133.

Ramadani RD, Utomo RY, Hermawan A, Meiyanto E. 2021. Pentagamaboronon­0­Sorbitol induces apoptosis through elevation of reactive oxygen species in triple negative breast cancer cells. Indones. J. Cancer Chemoprevention 12(1):46–56. doi:10.14499/indonesianjcanchemoprev12iss1pp46­ 56.

Ross JS, Slodkowska EA, Symmans WF, Pusztai L, Ravdin PM, Hortobagyi GN. 2009. The HER2 receptor and breast cancer: Ten years of targeted anti–HER2 therapy and personalized medicine. The Oncologist 14(4):320–368. doi:10.1634/theoncologist.2008­0230.

Shangguan L, Q C, B S, F H. 2017. Enhancing the solubility and bioactivity of anticancer drug tamoxifen by water­soluble pillar[6]arene­based host­guest complexation. Chem. Commun. 53(70):9749–9752. doi:10.1039/c7cc05305c.

Trachootham D, Alexandre J, Huang P. 2009. Targeting cancer cells by ROS­mediated mechanisms: A radical therapeutic approach? Nat. Rev. Drug Discovery 8(7):579–591. doi:10.1038/nrd2803.

Utomo RY, Putri H, Pudjono, Susidarti RA, Jenie RI, Meiyanto E. 2017. Synthesis and cytotoxic activity of 2,5­bis(4­boronic acid)benzylidine cyclopentanone on HER2 overexpressedcancer cells. Indones. J. Pharm. 28(2):74–81. doi:10.14499/indonesianjpharm28iss2pp74.

Waalkes S, Eggers H, Blasig H, Atschekzei F, Kramer MW, Hennenlotter J, Tränkenschuh W, Stenzl A, Serth J, Schrader AJ, Kuczyk MA, Merseburger AS. 2011. Caveolin 1 mRNA is overexpressed in malignant renal tissue and might serve as a novel diagnostic marker for renal cancer. Biomarkers Med. 5(2):219– 225. doi:10.2217/bmm.11.12.

Yokoyama H, Ikehara Y, Kodera Y, Ikehara S, Yatabe Y, Mochizuki Y, Koike M, Fujiwara M, Nakao A, Tatematsu M, Nakanishi H. 2006. Molecular basis for sensitivity and acquired resistance to gefitinib in HER2­overexpressing human gastric cancer cell lines derived from liver metastasis. Br. J. Cancer 95(11):1504–1513. doi:10.1038/sj.bjc.6603459.

Zhu Y, Bu S. 2017. Curcumin induces autophagy, apoptosis, and cell cycle arrest in human pancreatic cancer cells. Evid. Based. Complement. Alternat. Med. 2017:1–13. doi:10.1155/2017/5787218.



DOI: https://doi.org/10.22146/ijbiotech.67549

Article Metrics

Abstract views : 2039 | views : 1712

Refbacks

  • There are currently no refbacks.


Copyright (c) 2022 The Author(s)

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.