Curcumin induces apoptosis in trophoblast model cell line

  • Tatit Nurseta Department of Obstetric and Gynecology, Faculty of Medicine, Universitas Brawijaya, Malang
  • Yahya Irwanto Division of Oncology Gynecology, Department of Obstetric and Gynaecology, Saiful Anwar Hospital, Faculty of Medicine, Universitas Brawijaya, Malang
  • I W.A. Wiyasa Division of Fertility, Endocrinology and Reproduction, Obstetric and Gynaecology Laboratory, Saiful Anwar Hospital, Faculty of Medicine, Universitas Brawijaya, Malang
  • Rahajeng Rahajeng Division of Urogynecology, Obstetric and Ginaecology Laboratory, Saiful Anwar Hospital, Faculty of Medicine, Universitas Brawijaya, Malang
  • Imelda Imelda Resident of Obstetric and Gynaecology, Saiful Anwar Hospital, Faculty of Medicine, Universitas Brawijaya, Malang
  • Putu A.R. Ratnawati Resident of Obstetric and Gynaecology, Saiful Anwar Hospital, Faculty of Medicine, Universitas Brawijaya, Malang
Keywords: apoptosis, curcumin, eNOS, hydatidiform mole, trophoblast
Abstract viewed: 1029 times
PDF downloaded: 668 times
HTML downloaded: 120 times
EPUB downloaded: 135 times


Background: Several studies have reported that curcumin exerts chemopreventive effects in various type of cancers, through several mechanisms, however, the effect of curcumin on carcinogenesis in patients with hydatidiform mole has not yet been investigated. This study was conducted to evaluate the effect of curcumin on apoptosis, proliferation, and nuclear translocation of endothelial nitricoxide synthase in trophoblast cells induced by estradiol in complete hydatidiform mole (CHM).

Methods: In this in vitro study, trophoblast cells were divided into six groups, the control group (trophoblast cells were exposed to 100 pg/mL of 17-β estradiol) and the treatment group (trophoblast cells were exposed to 100 pg/mL of 17-β estradiol in the presence of curcumin with doses: 50, 100, 200, 400, and 800 μM). At the end of study, the cell proliferation was analyzed using MTT assay and apoptosis with TUNEL test in each group thropoblast cell. eNOS translocation was assayed using confocal laser scanning microscopy at the various dose of curcumin.

Results: Curcumin at the doses of 200, 400, and 800 μM significantly decreased the proliferation and increased the apoptotic index in curcumin-treated group compared to those in the control group (p<0.05). All doses of curcumin treatment significantly decreased the nuclear eNOS expression compared to that in the control group. The three highest doses of curcumin increased cytoplasmic eNOS expression compared to that in control group.

Conclusion: Curcumin inhibits the proliferation and modulates the apoptosis of trophoblast cells induced by estradiol in CHM involvement.


Download data is not yet available.


  1. Strohl A, Lurain J. Clinical epidemiology of gestational trophoblastic disease. Curr Obstet Gynecol Rep. 2014;3:40-3.

  2. Chen KH, Hsu SC, Chen HY, Ng KF, Chen TC. Utility of fluorescence in situ hybridization for ploidy and p57 immunostaining in discriminating hydatidiform moles. Biochem Biophys Res Comm. 2014;446:555-60.

  3. Shupnik MA. Crosstalk between steroid receptors and the c-Src-receptor tyrosine kinase pathways: implications for cell proliferation. Oncogene. 2004;23(48):7979-89.

  4. Cheskis BJ, Greger J, Cooch N, McNally C, McLarney S, Lam HS, et al. MNAR plays an important role in ERa activation of Src/MAPK and PI3K/Akt signaling pathways. Steroids. 2008;73(9-10):901-15.

  5. Burke AJ, Sullivan FJ, Giles FJ, Glynn SA. The yin and yang of nitric oxide in cancer progression. Carcinogenesis. 2013;34(3):503-12.

  6. Ying L, Hofseth LJ. An Emerging role for endothelial nitric oxide synthase in chronic inflammation and cancer. Cancer Res. 2007;67(4):1407-10.

  7. Xun W, Zhi FW, Yin X, Rui R, Bao LH, Ze XS. Association between three eNOS polymorphisms and cancer risk: a meta-analysis. Asian Pac J Cancer Prev. 2014;15(13):531-24.

  8. Temiz C, Arslan M, Sayin M, Vatansever M, Giray G, Va A. Effects of nitric oxide-vascular endothelial growth factor systems in chick embryo cerebral vasculogenesis and angiogenesis. J Clin Anal Med. 2012;3(4):393-7.

  9. Barbieri A, Palma G, Rosati A, Giudice A, Falco A, Petrillo A, et al. Role of endothelial nitric oxide synthase (eNOS) in chronic stress-promoted tumour growth. J Cell Mol Med. 2012;16(4):920-6.

  10. Barut A, Harma M, Arikan I, Barut F. Endothelial nitric oxide synthase expression in gestational trophoblastic diseases. Int J Gynecol Cancer. 2010; 20(3):337-40.

  11. Lu Q, Schnitzler GR, Ueda K, Iyer LK, Diomede OI, Andrade T, et al. ER alpha rapid signaling is required for estrogen induced proliferation and migration of vascular endothelial cells. PLoS ONE. 2016;11(4): e0152807.

  12. Vanini F, Kashfi K, Nath N. The dual role of iNOS in cancer. Redox Biol. 2015;6:334-43.

  13. Zhou L, Wang Y, Tian D, Yang J, Yang Z. Decreased levels of nitric oxide production and nitric oxide synthase-2 expression are associated with the development and metastasis of hepatocellular carcinoma. Mol Med Rep. 2012;6(6):1261-6.

  14. Bandyopadhyay D. Farmer to pharmacist: curcumin as an anti-invasive and antimetastatic agent for the treatment of cancer. Front Chem. 2014;2:113.

  15. Wilken R, Veena MS, Wang MB, Srivatsan ES. Curcumin: a review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol Cancer. 2011;10:12.

  16. Noorafshan A, Ashkani-Esfahani S. A review of therapeutic effects of curcumin. Curr Pharm Des. 2013;19:2032â46.

  17. Abuelba H, Cotrutz CE, Stoica BA, Stoica L, Olinici D, Petreus T. In vitro evaluation of curcumin effects on breat adenocarcinoma 2D and 3D cultures. Rom J Morphol Embryol. 2015; 56(1):71-6.

  18. Jamalzadeh L, Ghafoori H, Sariri R, Rabati H, Nasirzade J, Hasani H. Cytotoxic effects of some common organic solvent on MCF-7, RAW-264.7 and human umbilical vein endothelial cells. Avicenna J Med Biochem. 2015;4(1):e33453.

  19. Acharya S, Reddy R, Kuppili, Chaganti KL, Bose K. Proteases in apoptosis: protocols and methods. in: bose k, editor.proteases in apoptosis: pathways, protocols and translational. 1st ed. Switzerland; Springer International Publishing; 2015. p. 143-202.

  20. Rajesh E, Sankari LS, Malathi M, Krupaa JR. Naturally occurring products in cancer therapy. J Pharm Bioallied Sci. 2015;7(Suppl 1):S181-S3.

  21. Park W, Amin AR, Chen ZG, Shin DM. New perspectives of curcumin in cancer prevention. Cancer Prev Res (Phila). 2013;6(5):387-400.

  22. Du Y, Feng J, Wang RM, Zhang H, Liu J. Effects of flavonoids from Potamogeton crispus L. on proliferation, migration, and invasion of human ovarian cancer cells. PLoS One. 2015; 10(6): e0130685.

  23. Mahmud M, Diwoni A, Filiczak N, Janicka M, Gubernatus J. Long-circulating curcumin-loaded liposome formulations with high incorporation effeciency, stability and anticancer activity towards pancreatic adenocarcinoma cell lines in vitro. PLoS One. 2016. 10:1371.

  24. Notarbartolo M, Poma P, Perri D, Dusonchet L, Cervello M, D'Alessandro N. Antitumor effects of curcumin, alone or in combination with cisplatin or doxorubicin, on human hepatic cancer cells. Analysis of their possible relationship to changes in nuclear factor-kappaB (NF-kB) activation levels and in inhibitory of apoptosis proteins (IAP) gene expression. Cancer Letters. 2005;224(1):53-65.

  25. Nanni S, Aiello A, Re A, Guffanti A, Benvenuti V, Collusi C. Estrogen-dependent dynamic profile of eNOS-DNA assosiations in prostate cancer. PLoS One. 2013. 10:371-79.

How to Cite
Nurseta T, Irwanto Y, Wiyasa IW, Rahajeng R, Imelda I, Ratnawati PA. Curcumin induces apoptosis in trophoblast model cell line. Med J Indones [Internet]. 2018Sep.9 [cited 2024Jul.16];27(2):87–93. Available from:
Basic Medical Research