scholarly journals Hydroethanolic Extracts of the Aristotelia Chilensis (Maqui) Berry Reduces Cellular Viability and Invasiveness in the Endometrial Cancer Cell Line Ishikawa

2021 ◽  
Vol 20 ◽  
pp. 153473542110075
Author(s):  
Javier Mena ◽  
Estefanía Elgueta ◽  
Francisca Espinola-Gonzales ◽  
Hugo Cardenas ◽  
Pedro A. Orihuela

Cancer of the reproductive tract includes diseases with higher prevalence in the female population. This investigation examined whether an anthocyanin-enriched extract of Aristotelia chilensis, commonly known as “maqui,” could affect some hallmarks of endometrial cancer. Cultures of the human endometrial cancer cell line Ishikawa were treated with a hydroethanolic maqui extract at 1, 3, 10, 30, 100, 300, or 1000 µg/mL to determine the effect on cell viability by MTT assay. Then, we used the 50% Effective Concentration (EC50) to evaluate whether the effect of the maqui extract is mediated via an arrest of the cell cycle or induction of apoptosis using flow cytometry or Annexin V-FITC assays, respectively. The effects of sublethal doses of the maqui extract on migration and invasiveness of Ishikawa cells were also evaluated by the wound healing and Boyden Chamber assay, respectively. Our results show that the hydroethanolic maqui extract inhibits the cell viability with an EC50 of 472.3 µg/mL via increased apoptosis, and that reduces the invasive capacity but not migration of Ishikawa cells. These findings suggest that the hydroethanolic maqui extract has antineoplastic properties for endometrial cancer and merits further studies to corroborate its efficiency as anticancer therapy in reproductive organs.

2019 ◽  
Vol 20 (16) ◽  
pp. 3850 ◽  
Author(s):  
Ramiro Rincón-Rodriguez ◽  
Dennise Mena ◽  
Javier Mena ◽  
Patricia Díaz-Saldivar ◽  
Emanuel Guajardo-Correa ◽  
...  

The metabolite 2-methoxyestradiol (2ME) is an endogenous estrogen metabolite with potential therapeutic properties in reproductive cancers. However, the molecular mechanisms by which 2ME exerts its anticancer activity are not well elucidated. The purpose of this study was to determine the molecular signals associated with the apoptotic effects of 2ME in a human endometrial cancer cell line. Ishikawa cells were treated with non-apoptotic (0.1 µM) or apoptotic concentrations (5 µM) of 2ME, and 12 hours later mRNA levels for Scd2, Snx6, and Spon1 were determined by real-time PCR. We then investigated by immunofluorescence and Western blot the expression and distribution of F-spondin, encoded by Spon1, in Ishikawa cells treated with 2ME 5 µM at 6, 12, or 24 h after treatment. The role of estrogen receptors (ER) in the effect of 2ME on the Spon1 level was also investigated. Finally, we examined whether 2ME 5 µM induces cell death in Ishikawa cells pre-incubated with a neutralizing F-spondin antibody. Non-apoptotic or apoptotic concentrations of 2ME decreased Scd2 and increased Snx6. However, Spon1 was only increased with the 2ME apoptotic concentration. F-spondin protein was also increased at 12 and 24 h after 2ME treatment, while 2ME-induced Spon1 increase was independent of ER. Neutralization of F-spondin blocked the effect of 2ME on the cell viability. These results show that F-spondin signaling is one of the components in the apoptotic effects of 2ME on Ishikawa cells and provide experimental evidence underlying the mechanism of action of this estrogen metabolite on cancer cells.


Author(s):  
Ryou Misao ◽  
Yoshihito Nakanishi ◽  
Jiro Fujimoto ◽  
Teruhiko Tamaya

The effect of progestins on intracellular corticosteroid-binding globulin (CBG) mRNA expression in an endometrial cancer cell line (Ishikawa) was examined in an attempt to understand the biological effects of high-dose progestins in the treatment of well-differentiated uterine endometrial cancers. Oestradiol-17β (E2) significantly increased CBG mRNA expression in a dose-dependent manner, while a high dose of progesterone with or without E2 suppressed it significantly. Furthermore, a high dose of progesterone or medroxyprogesterone acetate (MPA) suppressed CBG mRNA expression to a greater degree than did chlormadinone acetate or 17 α-hydroxyprogesterone caproate with or without E2. These findings suggest that the effects of high-dose progestins on cancer cells may be mediated via suppression of intracellular CBG.


Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1273 ◽  
Author(s):  
Rajani Rai ◽  
Kathleen Gong Essel ◽  
Doris Mangiaracina Benbrook ◽  
Justin Garland ◽  
Yan Daniel Zhao ◽  
...  

Sulforaphane exerts anti-cancer activity against multiple cancer types. Our objective was to evaluate utility of sulforaphane for endometrial cancer therapy. Sulforaphane reduced viability of endometrial cancer cell lines in association with the G2/M cell cycle arrest and cell division cycle protein 2 (Cdc2) phosphorylation, and intrinsic apoptosis. Inhibition of anchorage-independent growth, invasion, and migration of the cell lines was associated with sulforaphane-induced alterations in epithelial-to-mesenchymal transition (EMT) markers of increased E-cadherin and decreased N-cadherin and vimentin expression. Proteomic analysis identified alterations in AKT, mTOR, and ERK kinases in the networks of sulforaphane effects in the Ishikawa endometrial cancer cell line. Western blots confirmed sulforaphane inhibition of AKT, mTOR, and induction of ERK with alterations in downstream signaling. AKT and mTOR inhibitors reduced endometrial cancer cell line viability and prevented further reduction by sulforaphane. Accumulation of nuclear phosphorylated ERK was associated with reduced sensitivity to the ERK inhibitor and its interference with sulforaphane activity. Sulforaphane induced apoptosis-associated growth inhibition of Ishikawa xenograft tumors to a greater extent than paclitaxel, with no evidence of toxicity. These results verify sulforaphane’s potential as a non-toxic treatment candidate for endometrial cancer and identify AKT, mTOR, and ERK kinases in the mechanism of action with interference in the mechanism by nuclear phosphorylated ERK.


1997 ◽  
Vol 99 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Jin-Woo Kim ◽  
Chun-Geun Lee ◽  
Soo-Kyung Choi ◽  
Jae-Hoon Kim ◽  
Tae-Eung Kim ◽  
...  

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