scholarly journals Anticancer Effects of Propionic Acid Inducing Cell Death in Cervical Cancer Cells

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4951
Author(s):  
Chau-Ha Pham ◽  
Joo-Eun Lee ◽  
Jinha Yu ◽  
Sung-Hoon Lee ◽  
Kyung-Rok Yu ◽  
...  

Recent studies found that short-chain fatty acids (SCFAs), which are produced through bacterial fermentation in the gastrointestinal tract, have oncoprotective effects against cervical cancer. The most common SCFAs that are well known include acetic acid, butyric acid, and propionic acid, among which propionic acid (PA) has been reported to induce apoptosis in HeLa cells. However, the mechanism in which SCFAs suppress HeLa cell viability remain poorly understood. Our study aims to provide a more detailed look into the mechanism of PA in HeLa cells. Flow cytometry analysis revealed that PA induces reactive oxygen species (ROS), leading to the dysfunction of the mitochondrial membrane. Moreover, PA inhibits NF-κB and AKT/mTOR signaling pathways and induces LC3B protein levels, resulting in autophagy. PA also increased the sub-G1 cell population that is characteristic of cell death. Therefore, the results of this study propose that PA inhibits HeLa cell viability through a mechanism mediated by the induction of autophagy. The study also suggests a new approach for cervical cancer therapeutics.

Author(s):  
Nuraeni Ekowati ◽  
Aris Mumpuni ◽  
Juni Safitri Muljowati

<p><em>Pleurotus ostreatus</em> is a common mushroom cultivated in Indonesia, and potential properties of bioactive compounds for medicinal mushroom. This study was aimed at obtaining <em>P.ostreatus</em> extract bioactive compounds potential in inhibiting the proliferation of cervical cancer cells (HeLa) and evaluating the HeLa cell proliferation kinetics and HeLa cell death mechanisms. The research was beneficial in making this product can be easily applied in a more controlled industrial scale. Anticancer activity test through a cytotoxic test using the MTT [3- (4,5-dimetiltiazol-2-yl) -2.5-diphenyl tertrazolium bromide], the kinetics proliferation of HeLa cells and HeLa cell death mechanism was performed. Linear regression analysis was used to analyze the data. Ethyl acetate extract of <em>P.</em> <em>ostreatus</em> isolated from Madiun showed the best results with IC <sub>50</sub> = 107.59 µg / ml. HeLa cell proliferation kinetics analysis showed that the application of bioactive compounds 100 µg / ml resulted in an increase of in death of HeLa cells along with length of incubation time. An important finding was that HeLa cells death by apoptosis was greater than by necrosis.  In conclusion, the extracts of <em>P.</em> <em>ostreatus</em>  has the potential to inhibit the growth of HeLa cells.</p><p> </p>


2020 ◽  
pp. 4-7
Author(s):  
M. R. Kamala Priya ◽  
Priya R. Iyer

Doxorubicin is the most common chemotherapy drug used in cancer therapy. Its usage is associated with various side-effects. In order to overcome the challenges in Doxorubicin administration, the present study has focussed on synthesizing a drug conjugate with biosynthesized gold nanoparticles and doxorubicin. The gold nanoparticles were biosynthesized using green extracts of medicinal plants with potential anticancer activities. The nanoparticle that possesses anticancer activity was conjugated with the drug for a combinatorial effect of the nanoparticles and the drug. The in vitro cytotoxicity was checked in Vero cell line through MTT assay. The in vitro anti proliferative effects were screened against cervical cancer in HeLa cell line. Fluorescence activated cell sorting analysis was carried out to detect the difference between live and dead cell populations. The preliminary confirmation was carried out in UV-VIS spectrophotometer. The morphological characterization was carried out by SEM and stability by Zeta potential. The IC50 of the nanocompounds demonstrated anti-proliferative activity against cervical cancer similar to the chemotherapeutic drug, Doxorubicin; additionally in a much lesser concentration of the drug. The in vitro cytotoxicity exhibited high viability of cells in Vero cell line with minimum viability of 80% in all the tested concentrations. There was a synergistic effect of the nanoparticles along with the drug; thereby an enhanced therapeutic efficiency was achieved. FACS analysis showed 36% of cell death in Dox treated HeLa cells whereas 96% of cell death in Nano-Dox treated HeLa cells. Nano-Dox conjugate has demonstrated high anticancer effects than drug alone Doxorubicin. Further biosynthesized nanomaterials based drug formulation can be developed as a potential strategy in cancer therapy.


Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1586
Author(s):  
Sera Kayacan ◽  
Kaan Yilancioglu ◽  
Ayse Seda Akdemir ◽  
Fatma Kaya Dagistanli ◽  
Gulay Melikoglu ◽  
...  

: Cervical cancer is one of the frequent types of cancer seen in females. It has been suggested that natural compounds can be used effectively for cancer treatment. Apoptosis and autophagy related cell death play important roles in suppression of tumorigenesis. Apigenin and curcumin are natural products isolated from plant extracts known to have antitumoral, antibacterial and antiviral effects. Varying doses of curcumin and apigenin were applied to HeLa cancer cell lines. The expression of the genes related to apoptosis and/or autophagy related cell death were measured using qRT-PCR and cell viability was measured using MTT assay. Our results showed that curcumin and apigenin are effective on apoptosis and autophagy related cell death in HeLa cells. We suggested that these natural products seem to be a new promising therapeutic approach in cancer.


2018 ◽  
Vol 96 (10) ◽  
pp. 1004-1011 ◽  
Author(s):  
Zita Bognar ◽  
Katalin Fekete ◽  
Rita Bognar ◽  
Aliz Szabo ◽  
Reka A. Vass ◽  
...  

Previously, we found that desethylamiodarone (DEA) may have therapeutic potentiality in bladder cancer. In this study, we determined its effects on human cervical cancer cells (HeLa). Cell viability was evaluated by Muse Cell Count & Viability Assay; cell apoptosis was detected by Muse Annexin V & Dead Cell Assay. Cell cycle was flow cytometrically determined by Muse Cell Cycle Kit and the morphological changes of the cells were observed under a fluorescence microscope after Hoechst 33342 staining. The changes in the expression levels of apoptosis-related proteins in the HeLa cells were assessed by immunoblot. Our results showed that DEA significantly inhibited the proliferation and viability of HeLa cells and induced apoptosis in vitro in dose-dependent and also in cell cycle-dependent manner because DEA induced G0/G1 phase arrest in the HeLa cell line. We found that DEA treatment downregulated the expression of phospho-Akt and phospho-Bad. In addition, DEA could downregulate expression of Bcl-2, upregulate Bax, and induce cytochrome c release. Our results indicate that DEA might have significance as an anti-tumor agent against human cervical cancer.


2020 ◽  
Author(s):  
Ru-pin Alicia Chi ◽  
Pauline van der Watt ◽  
Wei Wei ◽  
Michael Birrer ◽  
Virna Leaner

Abstract Background: Inhibition of nuclear import via Karyopherin beta 1 (Kpnβ1) shows potential as an anti-cancer approach. This study investigated the use of nuclear import inhibitor, INI-43, in combination with cisplatin. Methods: Cervical cancer cells were pre-treated with INI-43 before treatment with cisplatin, and MTT cell viability and apoptosis assays performed. Activity and localisation of p53 and NFκB was determined after co-treatment of cells.Results: Pre-treatment of cervical cancer cells with INI-43 at sublethal concentrations enhanced cisplatin sensitivity, evident through decreased cell viability and enhanced apoptosis. Kpnβ1 knock-down cells similarly displayed increased sensitivity to cisplatin. Combination index determination using the Chou-Talalay method revealed that INI-43 and cisplatin engaged in synergistic interactions. p53 was found to be involved in the cell death response to combination treatment as its inhibition abolished the enhanced cell death observed. INI-43 pre-treatment resulted in moderately stabilized p53 and induced p53 reporter activity, which translated to increased p21 and decreased Mcl-1 upon cisplatin combination treatment. Furthermore, cisplatin treatment led to nuclear import of NFκB, which was diminished upon pre-treatment with INI-43. NFκB reporter activity and expression of NFκB transcriptional targets, cyclin D1, c-Myc and XIAP, showed decreased levels after combination treatment compared to single cisplatin treatment and this associated with enhanced DNA damage. Conclusions: Taken together, this study shows that INI-43 pre-treatment significantly enhances cisplatin sensitivity in cervical cancer cells, mediated through stabilization of p53 and decreased nuclear import of NFκB. Hence this study suggests the possible synergistic use of nuclear import inhibition and cisplatin to treat cervical cancer.


2019 ◽  
Vol 12 (10) ◽  
pp. 1616-1623
Author(s):  
Annise Proboningrat ◽  
Amaq Fadholly ◽  
Regina Purnama Dewi Iskandar ◽  
Agung Budianto Achmad ◽  
Fedik Abdul Rantam ◽  
...  

Background and Aim: Cervical cancer accounts for the fourth as a cause of death from cancer in women worldwide, with more than 85% of events and deaths occurring in developing countries. The main problems of chemotherapy are the lack of selectivity and drug resistance. This study aimed to investigate the signal transduction of chitosan-based Pinus merkusii bark extract nanoparticles (Nano-PMBE) as an anticancer on HeLa cell line. Materials and Methods: Nano-PMBE was prepared based on the ionic gelation method. Its anticancer activities in HeLa cells were investigated through cytotoxicity test, cell cycle, and apoptosis analysis. The expression of p53 and caspase-9 was also observed. Results: The results showed that Nano-PMBE has a size of 394.3 nm. Meanwhile, the Nano-PMBE was cytotoxic to HeLa cells ( IC50 of 384.10 μg/ml), caused G0/G1 phase arrest and cell apoptosis in HeLa cells. Besides, the expression of p53 and caspase-9 has increased. Conclusion: The results showed a notable anticancer effect of Nano-PMBE by arresting the cell cycle and inducing apoptosis in HeLa cells, suggesting that it might have therapeutic potential for cervical cancer. Further research is needed to find out more about the anticancer mechanism of Nano-PMBE in HeLa cells to in vivo and clinical studies.


2020 ◽  
Author(s):  
Leilei Xu ◽  
Qin Zhang ◽  
Changhua Li ◽  
Fu Hua ◽  
Xiaoping Liu

Abstract Background: The gene-loaded microbubbles (MBs) combined with ultrasound resulting in increased delivery efficiency, may be a novel method of gene delivery. We explored the effects of ultrasound and microbubbles (USMB)-mediated microRNA (miR)-505 on cervical cancer (CC) development.Methods: miR-505 mediated by USMB was prepared. The effect of miR-505 on its transfection efficiency was studied by RT-qPCR. The effect of miR-505 on HeLa cell proliferation was evaluated by MTT and colony formation assays. Flow cytometry was used to study cell cycle changes, Hoechst was utilized to detect apoptosis. Through the wound healing and Transwell assay, the migration and invasion ability of HeLa cells were measured. The target gene of miR-505 was predicted, and its expression in CC was detected. The target relationship and the effect of the target gene on HeLa cells were further verified.Results: USMB-miR-505 showed higher transfection efficiency than miR-505 alone. miR-505 inhibited HeLa cell malignant episodes, which were reinforced by USMB treatment. miR-505 targeted AKT2. AKT2 was highly expressed in CC, and overexpression of AKT2 significantly reversed the inhibitory effect of miR-505 mediated by USMB on HeLa cell malignant biological behaviors.Conclusion: USMB-miR-505 inhibited HeLa cell malignant biological behaviors by targeting AKT2.


2020 ◽  
Author(s):  
Xiaofei Jiang ◽  
Mingqing Shi ◽  
Miao Sui ◽  
Yizhen Yuan ◽  
Shuang Zhang ◽  
...  

Abstract Background: Cervical cancer continues to be the leading cause of cancer deaths among women worldwide. Oleanolic acid (OA) is a naturally occurring substance found in the leaves, fruits, and rhizomes of plants that has anti-cancer activity. Methods: We used tumor-bearing mice as the animal model and Hela cell as cell models. Western blot was used for detecting the expression of proteins in ferroptosis related proteins acyl-CoA synthase long-chain family member 4 (ACSL4), ferritin heavy chain (FTH1), transferrin receptor (TfR1) and glutathione peroxidase 4 (GPX4) in vivo and in vitro. MTT and EdU was for the detection of the viability of Hela cells. Results: In vivo experiments showed that OA significantly reduced the size and mass of cervical cancer tumors. In vitro experiments showed that OA significantly reduced the viability and proliferation capacity of Hela cells. In both in vivo and in vitro assays, OA increased the level of oxidative stress and Fe2+ content, and increased the expression of ferroptosis related proteins. We found high expression of ACSL4 in both xenograft models and cervical carcinoma cells. Meanwhile, knockdown of ACSL4 expression using shRNA in cervical cancer cells significantly increased cell viability and proliferation. In addition, decreased ROS levels and GPX4 were detected in ACSL4 knockdown cervical cancer cells, suggesting that ACSL4 inhibition may contribute to the reduction of ferroptosis within Hela cells and thus improve Hela cell survival. Conclusion: Promotion of ACSL4 dependent ferroptosis through OA may be an effective approach to treat cervical cancer.


2019 ◽  
Vol 8 (3) ◽  
pp. 319-327
Author(s):  
Faramarz Rahmatizadeh ◽  
Fatima Pashaei-Asl ◽  
Manijeh Mohammadi Dehcheshmeh ◽  
Sara Rahbar ◽  
Maryam LaleAtaei ◽  
...  

Objectives: This experiment was carried out to evaluate the impacts of unmodified human amniotic fluid-derived mesenchymal stromal/stem cells (hAF-MSCs) on the viability of HeLa cells, as well as the impact of these cells on the expression of common proapoptotic and pro-survival genes in tumor cells by establishing an indirect co-culture system. Materials and Methods: To this end, an indirect co-culture system was established, and hAF-MSCs were co-cultured with HeLa cells at a ratio of 1:2 for five days. The cell viability of co-cultured tumor cells was determined after the incubation period. Then, several parameters were examined, including the gene expression of tumor protein 53 (TP53), BCL2-associated X protein (BAX), B-cell lymphoma 2 (BCL-2), and cyclin-dependent kinase inhibitor 1A (CDKN1A). Finally, gene regulatory networks were analyzed as well. Results: The results of this study confirmed that the co-culture of hAF-MSCs with HeLa cells could decrease the viability of tumor cells. The reduction of HeLa cell viability was accompanied by an increase in BAX, TP53, and CDKN1A while a decrease in BCL2 gene expression. Eventually, the analysis of the regulatory network revealed that the co-culture of Hela ¬cells with hAF-MSCs activated several transcriptional factors and microRNAs which regulated the expression of these genes. Conclusions: In general, hAF-MSCs exerted the inhibitive effects on the growth of HeLa cells, along with alterations in the expression of common pro-apoptotic and pro-survival genes in a timely and concentration-dependent manner.


2020 ◽  
Vol 19 (3) ◽  
pp. 467-474
Author(s):  
Alejandro Zugasti ◽  
Ana L. Rivera ◽  
Sonia Y. Silva ◽  
Miguel A. Alfaro ◽  
Crystel A. Sierra

Purpose: To evaluate the synergistic cytotoxicity of sodium dichloroacetate (DCA) in combination with cisplatin (CIS) against human cervical cancer cell lines. Methods: Cervical cancer SiHa and HeLa cells and normal cells (Hek-293, Vero, peripheral blood mononuclear and human erythrocytes) were treated in vitro with DCA and CIS individually or their combination. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method while hemolytic activity was evaluated from the released hemoglobin. Halfmaximal inhibitory concentration (IC50) of DCA or CIS was obtained. Results: The combination of DCA + CIS decreased the cell viability of SiHa, Hek-293, Vero, and PBMC cells, but not of Hela cells (p < 0.05). Furthermore, the individual treatments alone or in combination did not cause significant hemolysis (p < 0.05). Conclusion: The combination of DCA + CIS increases the damage caused by CIS alone on SiHa cells. It also decreases the cell viability of Hek-293 and Vero without affecting peripheral blood mononuclear and human erythrocyte integrity. The results suggest that the combination of DCA and CIS can induce synergistic antitumor effect in different types of cancer cell lines. However, further studies are required to determine the biological effects of the combination of DCA and CIS in vivo. Keywords: Cervical cancer, Sodium dichloroacetate, Cisplatin, Viability, Hemolysis


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