Anti-ovarian Cancer Activity Research Articles

QSCR Analysis of Cytotoxicity of 6-Fluoro-3-(4H-1,2,4-triazol-3- yl)quinolin-4(1H)-ones on Chinese Hamster Ovary Cell Line: Design of REPUBLIC1986.

6-Fluoro-3-(4H-1,2,4-triazol-3-yl)quinolin-4(1H)-ones are promising antitumor agents with enormous data on their profound cytotoxic effects on the human cancer cell lines. We sought to perform a Quantitative structure cytotoxicity relationship (QSCR) analysis of a series of previously reported fluoroquinolone analogues using computerassisted multiple regression analysis and investigate the cytotoxicity-inducing structural parameters among these congeners. The dataset was segregated into training and test sets of 6-Fluoro-3-(4H-1,2,4- triazol-3-yl)quinolin-4(1H)-ones by using a random selection method embedded in Vlife MDS 4.6 software and subjected to QSCR analysis. Next, cross-validation of the generated QSCR models was performed along with the external test set prediction. Finally, the data was analyzed and contour plots were developed to deduce the cytotoxicity-inducing structural parameters among these congeners using Minitab® software. The validated QSCR model exhibited a statistically significant predictive value of 92.27 percent. Our QSCR model revealed a direct proportionality between hydrogen counts and cytotoxicity, and exclusion of sulphur and nitrogen with lesser crowding of cyclopropyl rings in future potential 6-Fluoro-3-(4H-1,2,4-triazol-3-yl)quinolin-4(1H)-one analogues. Based on the QSCR model predictions and contour plot analysis, the de novo REPUBLIC1986 molecule provided the best hit with predicted IC50 (μM) of 0.45 against CHO cell line and is amenable to salt formation crucial for anti-ovarian cancer activity. These findings suggest the relevancy of the developed QSCR model in designing novel, potent, and safer anti-cancer drugs with 6-Fluoro-3-(4H-1,2,4-triazol-3-yl)quinolin- 4(1H)-ones as seed compounds.

Green synthesis of nickel nanoparticles using Fumaria officinalis as a novel chemotherapeutic drug for the treatment of ovarian cancer

In the present study, nickel nanoparticles were green-synthesized using the aqueous extract of Fumaria officinalis. The synthesized NiNPs@F. officinalis were characterized by analytical techniques including EDX, FE-SEM, XRD, UV-Vis., and FT-IR. The antioxidant and anti-ovarian cancer activity of NiNPs@F. officinalis was evaluated. The nanoparticles were formed in a spherical shape in the range of 16.85 to 49.04 nm for the particle size. In the antioxidant test, the IC50 of F. officinalis, NiNPs@F. officinalis, and BHT against DPPH free radicals were 253, 145, and 107 µg/mL, respectively. In the cellular and molecular part of the recent study, the treated cells with NiNPs@F. officinalis were assessed by MTT assay for 48 h about the cytotoxicity and anti-human ovarian cancer properties on normal (HUVEC) and ovarian cancer cell lines i.e. PA-1, Caov-3, SW-626, and SK-OV-3. The viability of malignant ovarian cell line reduced dose-dependently in the presence of NiNPs@F. officinalis. The IC50 of NiNPs@F. officinalis were 375, 225, 246, and 279 µg/mL against PA-1, Caov-3, SW-626, and SK-OV-3 cell lines, respectively. After the clinical study, nickel nanoparticles containing F. officinalis leaf aqueous extract may be used to formulate a new chemotherapeutic drug or supplement to treat several types of human ovarian cancer.

Biogenic and biocompatible silver nanoparticles for an apoptotic anti-ovarian activity and as polydopamine-functionalized antibiotic carrier for an augmented antibiofilm activity

Silver nanoparticles (AgNPs) could be employed in the combat against COVID-19, yet are associated with toxicities. In this study, biogenic and biocompatible AgNPs using the agro-waste, non-edible Hibiscus sabdariffa stem were synthesized. Under optimized reaction conditions, synthesized green AgNPs were crystalline, face cubic centered, spherical with a diameter of around 17 nm and a surface charge of −20 mV. Their murine lethal dose 50 (LD50) was 4 folds higher than the chemical AgNPs. Furthermore, they were more murine hepato- and nephro-tolerated than chemical counterparts due to activation of Nrf-2 and HO-1 pathway. They exerted an apoptotic anti-ovarian cancer activity with IC50 value 6 times more than the normal cell line. Being functionalized with polydopamine and conjugated to either moxifloxacin or gatifloxacin, the conjugates exerted an augmented antibiofilm activity against Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii biofilms that was significantly higher than antibiotic alone or functionalized AgNPs suggesting a synergistic activity. In conclusion, this study introduced a facile one-pot synthesis of biogenic and biocompatible AgNPs with preferential anti-cancer activity and could be utilized as antibiotic delivery system for a successful eradication of Gram-negative biofilms.

Trichodermin Induces G0/G1 Cell Cycle Arrest by Inhibiting c-Myc in Ovarian Cancer Cells and Tumor Xenograft-Bearing Mice.

Ovarian cancer is a fatal gynecological cancer because of a lack of early diagnosis, which often relapses as chemoresistant. Trichodermin, a trichothecene first isolated from Trichoderma viride, is an inhibitor of eukaryotic protein synthesis. However, whether trichodermin is able to suppress ovarian cancer or not was unclear. In this study, trichodermin (0.5 µM or greater) significantly decreased the proliferation of two ovarian cancer cell lines A2780/CP70 and OVCAR-3. Normal ovarian IOSE 346 cells were much less susceptible to trichodermin than the cancer cell lines. Trichodermin predominantly inhibited ovarian cancer cells by inducing G0/G1 cell cycle arrest rather than apoptosis. Trichodermin decreased the expression of cyclin D1, CDK4, CDK2, retinoblastoma protein, Cdc25A, and c-Myc but showed little effect on the expression of p21Waf1/Cip1, p27Kip1, or p16Ink4a. c-Myc was a key target of trichodermin. Trichodermin regulated the expression of Cdc25A and its downstream proteins via c-Myc. Overexpression of c-Myc attenuated trichodermin’s anti-ovarian cancer activity. In addition, trichodermin decelerated tumor growth in BALB/c nude mice, proving its effectiveness in vivo. These findings suggested that trichodermin has the potential to contribute to the treatment of ovarian cancer.

Investigation of anti-human ovarian cancer effects of decorated Au nanoparticles on Thymbra spicata extract modified Fe3O4 nanoparticles

This work describes an eco-friendly approach for in situ immobilization of Au nanoparticles on the surface of Fe3O4 nanoparticles, with the help of Thymbra spicata extract and ultrasound irradiations, without using any toxic reducing and capping agents. The combination of Fe3O4 NPs and Au NPs in one hybrid nanostructure (Fe3O4@Thymbra spicata/Au NPs) represents a promising strategy for targeted biomedical applications. The structure, morphology, and physicochemical properties were characterized by various analytical techniques such as fourier transformed infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), inductively coupled plasma (ICP) and vibrating sample magnetometer (VSM). MTT assay was used on common ovarian cancer cell lines i.e., SW-626, PA-1, and SK-OV-3 to survey the cytotoxicity and anti-ovarian cancer effects of Fe3O4@Thymbra spicata/Au NPs. The best results of cytotoxicity and anti-ovarian cancer properties were seen in the concentration of 1000 µg/mL. Fe3O4@ Thymbra spicata/Au NPs had very low cell viability and high anti-ovarian cancer activities dose-dependently against PA-1, SW-626, and SK-OV-3 cell lines without any cytotoxicity on the normal cell line (HUVEC). For investigating the antioxidant properties of Fe3O4@ Thymbra spicata/Au NPs, the DPPH test was used in the presence of butylated hydroxytoluene as the positive control. Fe3O4@Thymbra spicata/Au NPs inhibited half of the DPPH molecules in the concentration of 107 µg/mL. Maybe significant anti-human ovarian cancer potentials of Fe3O4@Thymbra spicata/Au NPs against common human ovarian cancer cell lines are linked to their antioxidant activities. After confirming the above results in the clinical trial researches, this formulation can be administrated for the treatment of several types of human ovarian cancers in humans.

Two Co(II) coordination polymers: crystal structures and anti-ovarian cancer activity by inducing the ROS genes expression

We, the Editors and Publisher of the journal Inorganic and Nano-Metal Chemistry, have retracted the following article: Dong-Mei Yang, Li-Hong Huang, Qiong Xia, Ai-Ling Li & Yu Chen. Two Co(II) coordination polymers: crystal structures and anti-ovarian cancer activity by inducing the ROS genes expression, Inorganic and Nano-Metal Chemistry, 2022. Volume 52: issue number 4, 608–613, DOI: 10.1080/24701556.2021.1916759 Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to address the concerns raised and have not been able to provide sufficient supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. The authors do not agree with the retraction. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Synthesis, anti-ovarian cancer activity evaluation and docking studies of pyran derivatives

The synthesis and characterization of new pyran derivatives (1–3) were realized by means of infrared spectroscopy (IR), 1H nuclearmagnetic resonance spectroscopy (1H NMR), high resolution mass spectrum (HRMS) and single crystal X-ray crystallography. The anti-proliferation activity of compounds 1–3 was investigated against human ovarian cancer cells CAOV3 by Cell Counting Kit-8 (CCK-8) assay. The RT-PCR assay was performed to detect the relative expression level of the Foxm1b in the CAOV3 cell line after treated with compounds 1–3. Furthermore, molecular docking studies supported the biological assay data and suggested that compared with compounds 1 and 3, compound 2 has stronger interaction with protein.

Green synthesis, characterization, cytotoxicity, antioxidant, and anti-human ovarian cancer activities of Curcumae kwangsiensis leaf aqueous extract green-synthesized gold nanoparticles

The present work indicated the green synthesis, characterization, cytotoxicity, antioxidant, and anti-human ovarian cancer activities of gold nanoparticles containing Curcumae Kwangsiensis Folium (Leaf) aqueous extract. Characterization of gold nanoparticles was done by Field Emission Scanning Electron Microscopy (FE‐SEM), Transmission Electron Microscopy (TEM), Fourier Transformed Infrared Spectroscopy (FT‐IR), and UV–Visible Spectroscopy (UV–Vis). MTT assay was used on common ovarian cancer cell lines i.e., SW-626, PA-1, and SK-OV-3 to survey the cytotoxicity and anti-ovarian cancer effects of gold chloride, Curcumae Kwangsiensis Folium leaf aqueous extract, and gold nanoparticles. The best results of cytotoxicity and anti-ovarian cancer properties were seen in the case of gold nanoparticles. They had very low cell viability and high anti-ovarian cancer activities dose-dependently against PA-1, SW-626, and SK-OV-3 cell lines without any cytotoxicity on the normal cell line (HUVEC). For investigating the antioxidant properties of gold chloride, Curcumae Kwangsiensis Folium leaf aqueous extract, and gold nanoparticles, the DPPH test was used in the presence of butylated hydroxytoluene as the positive control. The best results of antioxidant properties were seen in the case of gold nanoparticles. They inhibited half of the DPPH molecules in the concentration of 153 µg/mL. Maybe significant anti-human ovarian cancer potentials of gold nanoparticles synthesized by Curcumae Kwangsiensis Folium leaf aqueous extract against common human ovarian cancer cell lines are linked to their antioxidant activities.

20(S)-Rg3 upregulates FDFT1 via reducing miR-4425 to inhibit ovarian cancer progression

We previously found that ginsenoside 20(S)-Rg3 diminishes the proliferative and invasive capacities of ovarian cancer cells by decreasing miR-4425 level. Yet the mechanism of action of miR-4425 in ovarian cancer remains unclear. Here we report that miR-4425 is upregulated in ovarian cancer tissues relative to normal ovarian tissues, and transfection of miR-4425 inhibitor impairs the proliferation, migration and invasion of SKOV3 and 3AO ovarian cancer cells. Further, miR-4425 antagomiR reduces cell proliferation in a subcutaneous SKOV3 xenograft model using BALB/c nude mice. We identifies farnesyl-diphosphate farnesyltransferase 1 (FDFT1) as a direct target of miR-4425 by Western blotting and a luciferase reporter assay. Forced expression of FDFT1 via transfection of an FDFT1-expressing plasmid into ovarian cancer cells not only retards cell proliferation, motility and invasiveness, but also negates the tumorigenic properties of a miR-4425 mimic. By contrast, silencing of FDFT1 by siRNAs abrogates suppression of the proliferation, migration and invasion of ovarian cancer cells treated with a miR-4425 inhibitor. Finally, transfection of either a miR-4425 mimic or FDFT1 siRNAs into 20(S)-Rg3-treated ovarian cancer cells counteracts the tumor-inhibitory activity of the ginsenoside. In conclusion, 20(S)-Rg3 exerts anti-ovarian cancer activity by downregulating oncogenic miR-4425 that inhibits the expression of the tumor suppressor gene FDFT1. These results expand our current understanding of the molecular pathways leading to ovarian cancer progression, and unveil the mechanism of action of 20(S)-Rg3 in ovarian cancer inhibition.

Synthesis and crystal structure of two new Zn(II) and Ni(II) coordination polymers with anti-ovarian cancer activity

By using a mixed-ligand approach, two new coordination polymers with the chemical formula of {[Zn(L)(ip)·H2O]8}n (1, H2ip = isophthalic acid and L = 1,1’-(2-methylpropane-1,3-diyl)bis(1H-benzo[d]imidazole)) and {[Ni(L)(tdc)·2H2O]2}n (2, H2tdc = 2,5-thiophenedicarboxylic acid) have been hydrothermally synthesized and structurally characterized by single-crystal X-ray diffraction analyses, powder X-ray diffraction, thermogravimetric analysis and elemental analysis. In addition, in vitro anticancer activity of compounds 1 and 2 on four human ovarian cancer cells (CoC1, A2780, 3AO and OVCAR) was further determined. The results showed that compared with their organic ligands, the two compounds displayed efficient antitumor activity.

RETRACTED: Construction of two coordination polymers based on imidazolyl and aromatic dicarboxylic acid ligands: Structural diversity and anti-ovarian cancer activity study

This article has been retracted, and the online PDF has been watermarked “RETRACTION”. The retraction notice is available at http://doi.org/10.3233/MGC-220951.

RETRACTED ARTICLE: A porous Cu(II)-based metal-organic framework with one-dimensional hexagonal channels for solvent-free cyanosilylation and anti-ovarian cancer activity

On the basis of solvothermal reaction, a new porous Cu(II) metal-organic framework (MOF), {[(Cu(L)2(H2O)2](DMF)4)n (namely 1), can be formed via self-assembly of 3-(1H-pyrazol-4-yl)pyridine (namely HL) and Cu(II) ion in water and DMF mixed solvent. We characterized the MOF 1 via elemental analysis, powder X-ray diffraction (PXRD) and single crystal X-ray diffraction, thermogravimetric analysis (TGA) as well as Fourier-transform infrared spectra (FT-IR). In addition, MOF 1 can be used as a solvent free multiphase catalyst for cyanidation due to its open Cu(II) metal sites as well as a larger number of N atoms can be utilized as Lewis basic sites. In connection to these, the catalysis mechanism has also been discussed in detail. To explore the inhibitory function of compound 1a on Hey ovarian cancer cells viability, the CCK-8 was carried out, and the results revealed that compound 1a had good anti-cancer activity in vitro with the IC50 value of 2.81 ± 0.17 μg/mL. Besides, the anti-tumor mechanism of compound 1a was revealed by apoptosis and ROS detection, the results suggested that compound 1a anti-tumor activity owing to the inducing of cell apoptosis by increasing the ROS accumulation.

Improving the Anti-Ovarian Cancer Activity of Docetaxel by Self-Assemble Micelles and Thermosensitive Hydrogel Drug Delivery System.

In recent decades, a large number of research studies have been conducted to improve the treatment strategy against epithelial ovarian cancer, but women in advanced stage still have poor outcomes. The development of advanced treatments must be continued to overcome the limitation. Docetaxel, a semi-synthetic product derived from the Pacific Taxus extract, has been studied for many years for its potent anticancer applications. Aiming to solve the problems of its highly lipophilicity, insolubility and adverse side effects, nanocarriers were applied. Relying on the integration of nanoparticles which had optimized sizes, shapes, and surface properties, the effect of docetaxel was enhanced. In this study, we designed a novel drug loaded gel-forming nanoparticle system (Doc-NMs-hydrogel composites), which acted as a sustained drug depot for docetaxel. Docetaxel was encapsulated into MPEG-PCL and then into blank thermosensitive hydrogel Pluronic F-127. Characterization showed that the prepared Doc-NMs had high drug loading (7%), minor particle size (37 nm), relatively good water solubility. Moreover, the cytotoxicity, apoptosis induction and the antitumor effects of Doc-NMs-hydrogel composites on mice abdominal SKOV-3 ovarian cancer model were investigated in vivo. Compared with other groups, at the same dosage, Doc-NMs-hydrogel composites show better apoptosis induction and cell growth inhibition. In conclusion, the prepared Doc-NMs-hydrogel composites enhanced anti-tumor activity by increasing local docetaxel concentration, maintaining stable and sustained drug release, prolonging drug retention time in tumors, and reducing toxicity to normal tissues. Doc-NMs-hydrogel composites might have great potential clinical application in anti-ovarian cancer activity.

RETRACTED ARTICLE: Two Cd(II)-based coordination polymers constructed from different donor ligands: structural insights and anti-ovarian cancer activity evolution

We, the Editors and Publisher of the journal Inorganic and Nano-Metal Chemistry, have retracted the following article: Wen-Jun Li, Yu-Lai Gong, Wei Gou, Bo Li, Rui Wang & Zhen-Fang Lin. Two Cd(II)-based coordination polymers constructed from different donor ligands: structural insights and anti-ovarian cancer activity evolution, Inorganic and Nano-Metal Chemistry, 2020, VOL. 50, NO. 4, 222–228. DOI: 10.1080/24701556.2019.1706567 Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to address the concerns raised and have not been able to provide sufficient supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. The authors have agreed to the retraction. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

RETRACTED: New Ag(I) and Cu(I) coordination polymers containing N-donor ligands: Structural characterization and anti-ovarian cancer activity study

This article has been retracted, and the online PDF has been watermarked “RETRACTION”. The retraction notice is available at http://doi.org/10.3233/MGC-220954.

Synthesis and biological evaluation of celastrol derivatives as anti-ovarian cancer stem cell agents

Ovarian cancer is associated with a high percentage of recurrence of tumors and resistance to chemotherapy. Cancer stem cells (CSCs) are responsible for cancer progression, tumor recurrence, metastasis, and chemoresistance. Thus, developing CSC-targeting therapy is an urgent need in cancer research and clinical application. In an attempt to achieve potent and selective anti-CSC agents, a series of celastrol derivatives with cinnamamide chains were synthesized and evaluated for their anti-ovarian cancer activities. Most of the compounds exhibited stronger antiproliferative activity than celastrol, and celastrol derivative 7g with a 3,4,5-trimethoxycinnamamide side chain was found to be the most potent antiproliferative agent against ovarian cancer cells with an IC50 value of 0.6 μM. Additionally, compound 7g significantly inhibited the colony formation ability and reduced the number of tumor spheres. Furthermore, compound 7g decreased the percentage of CD44+, CD133+ and ALDH+ cells. Thus, compound 7g is a promising anti-CSC agent and could serve as a candidate for the development of new anti-ovarian cancer drugs.

Palmatine from Unexplored Rutidea parviflora Showed Cytotoxicity and Induction of Apoptosis in Human Ovarian Cancer Cells.

Ovarian cancer ranks amongst the deadliest cancers in the gynaecological category of cancers. This research work aims to evaluate in vitro anti-ovarian cancer activities and identify phytochemical constituents of a rarely explored plant species—Rutidea parviflora DC. The aqueous and organic extracts of the plant were evaluated for cytotoxicity using sulforhodamine B assay in four ovarian cancer cell lines and an immortalized human ovarian epithelial (HOE) cell line. The bioactive compounds were isolated and characterized by gas/liquid chromatography mass spectrometry and nuclear magnetic resonance spectroscopy. Caspase 3/7 activity assay, western blotting and flow cytometry were carried out to assess apoptotic effects of active compounds. The extracts/fractions of R. parviflora showed promising anti-ovarian cancer activities in ovarian cancer cell lines. A principal cytotoxic alkaloid was identified as palmatine whose IC50 was determined as 5.5–7.9 µM. Palmatine was relatively selective towards cancer cells as it was less cytotoxic toward HOE cells, also demonstrating interestingly absence of cross-resistance in cisplatin-resistant A2780 cells. Palmatine further induced apoptosis by increasing caspase 3/7 activity, poly-ADP-ribose polymerase cleavage, and annexin V and propidium iodide staining in OVCAR-4 cancer cells. Our studies warranted further investigation of palmatine and R. parviflora extracts in preclinical models of ovarian cancer.

Synthesis of (aminoalkyl)cycleanine analogues: cytotoxicity, cellular uptake, and apoptosis induction in ovarian cancer cells

Our previous studies demonstrated that cycleanine, a macrocyclic bisbenzylisoquinoline (BBIQ) alkaloid, showed potent anti-ovarian cancer activity via apoptosis induction. Here, we synthesized two novel (aminoalkyl)cycleanine analogues (2 and 3) through a simple and efficient two-step reaction starting from cycleanine isolated from Triclisia subcordata Oliv. These analogues showed greater potency than the unmodified cycleanine in three human ovarian cancer cell lines. Both 2 and 3 induced apoptosis in ovarian cancer cells by activations of caspases 3/7, cleavage of PARP, increase in subG1 cell cycle phase and in the percentage of apoptotic cells. Further confocal fluorescence microscopy analysis confirmed the cellular uptake of alkaloids in ovarian cancer cells by using the unique (alkynyl)cycleanine (3) via click chemistry reaction. Our results suggest that cycleanine could be a hit compound for the future development in attacking ovarian cancer.

Enhancing the anti-ovarian cancer activity of quercetin using a self-assembling micelle and thermosensitive hydrogel drug delivery system.

Ovarian cancer, as one of the killers that threaten women’s health, has been studied extensively. As a natural bioflavonoid with prospective effects, quercetin is highly recognized for its anti-cancer applications. However, one of the major challenges that quercetin faces is its poor water solubility, instability in physiological media, and subsequent poor bioavailability. Thus, optimizing the ideal drug delivery options is necessary to facilitate the harnessing of the maximum benefits from quercetin. In this study, a quercetin-loaded thermosensitive injectable hydrogel system (Qu-M–hydrogel composites) was constructed based on nanotechnology. Quercetin was encapsulated into MPEG-PCL (with a high drug loading of 7% and minor particle size of 32 nm) and then added into the blank thermosensitive hydrogel Pluronic F-127. The Qu-M–hydrogel composites showed a much slower release than Qu-M in vivo. Moreover, the cytotoxicity, apoptosis induction, and anti-tumor effects of the Qu-M–hydrogel composites on the abdominal SKOV-3 ovarian cancer mouse models were investigated in vivo. Compared with other groups, the Qu-M–hydrogel composites exhibited improved apoptosis induction and cell growth inhibition effects and in vivo trials showed a better balance between the anti-tumor efficacy in the Qu-M–hydrogel composite group than in other groups at an equal drug dose. In conclusion, the prepared Qu-M–hydrogel composites enhanced the anti-tumor activity by providing a high local quercetin concentration, sustained and stable drug release, extended drug retention inside the tumor, and low toxicity to normal tissues. The Qu-M–hydrogel composites might have great potential for clinical application in anti-ovarian cancer activity.

Sestrin2 and sestrin3 suppress NK-92 cell-mediated cytotoxic activity on ovarian cancer cells through AMPK and mTORC1 signaling.

Ovarian cancer is one of the major cancer types. NK-92 cell line, which has consistently and reproducibly high anti-tumor cytotoxicity, may be used for immunotherapy against ovarian cancer. Understanding the mechanisms that regulate the anti-tumor activity of NK-92 cells is important for developing novel therapeutic strategies. In the current study, using an ovarian cancer xenograft mouse model, we identified the up-regulation of sestrin2 (SESN2) and sestrin3 (SESN3) in intratumoral NK-92 cells. Lentivirus-transduced NK-92 cells, which overexpressed SESN2 or SESN3 after doxycycline treatment, exhibited less expression of activating receptors, perforin and granzyme B. Overexpression of SESN2 and SESN3 impaired tumoricidal effect of NK-92 cells both in vitro and in vivo. Furthermore, overexpression of SESN2 and SESN3 inhibited mTORC1 signaling while promoting AMPK signaling in NK-92 cells. Taken together, our data highlights the crucial effects of SESN2 and SESN3 on NK-92 cell-mediated anti-ovarian cancer activity. This study might be valuable for designing a novel therapeutic strategy for ovarian cancer.