scholarly journals Hesperidin Increase Cytotoxic Activity of Doxorubicin on Hela Cell Line Through Cell Cycle Modulation and Apoptotis Induction

Author(s):  
Indri Kusharyanti ◽  
Larasati Larasati ◽  
Ratna Asmah Susidarti ◽  
Edy Meiyanto

Combination of chemotherapeutic agent and chemopreventive agent is being a new approach in cancer treatment. This is aimed at enhancing the effectivity and also reducing drug resistance and adverse side effect of the chemotherapeutic agent. Hesperidin, a citrus flavonoid has reported to reduce the proliferation of many cancer cells. The objectives of this study were to investigate cytotoxic activities, cell cycle modulation and apoptosis induction of hesperidin and its combination with doxorubicin on Hela cell lines. MTT [3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide] assay was used to measure the growth inhibitory effect of hesperidin and its combination with doxorubicin on Hela cells. Cell cycle profile was determined by flowcytometry and the data obtained was analyzed by using ModFit LT 3.0 program. Apoptosis assay was done using double staining method using ethidium-bromide and acridine-orange. Hesperidin inhibited cell growth with IC50 48 μM, while the IC50 of doxorubicin was 1000 nM. Combination of 500 nM doxorubicin and 6 μM hesperidin showed strongest inhibitory effect toward Hela cells. Hesperidin of 24 µM accumulated HeLa cells at G1 phase, but its combination with 500 nM Doxorubicin gave G1 and S phase accumulation at 24 h incubation. Both of Hesperidin and Doxorubicin were capable of inducing apoptosis. In accordance of the apoptotic effect, hesperidin, doxorubicin and their combination decreased the expression Bcl-2 and increased the expression of Bax. According to this result, hesperidin has a potency to be developed as co-chemotherapeutic agent for cervical cancer.Keywords: Cochemotherapy, Hesperidin, Doxorubicin, Hela, MTT assay

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 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Leilei Xu ◽  
Qin Zhang ◽  
Changhua Li ◽  
Fu Hua ◽  
Xiaoping Liu

The application of ultrasound and microbubbles (USMB-) mediated microRNA (miR) is a promising approach of gene delivery for cancer treatment. We aimed to discuss the effects of USMB-miR-505 on cervical cancer (CC) development. miR-505 mediated by USMB was prepared. The effect of miR-505 on its transfection efficiency and the effect of miR-505 on HeLa cell proliferation, cell cycle, apoptosis, migration, and invasion were studied. The target gene of miR-505 was predicted, and its expression in CC was detected. The effect of the target gene on HeLa cells was further verified. USMB-miR-505 showed a higher transfection efficiency than miR-505 alone. The inhibitory effect of miR-505 mediated by USMB on HeLa cells was better than miR-505. miR-505 targeted AKT2, which was upregulated in CC. Overexpression of AKT2 reversed the inhibitory effect of USMB-miR-505 on HeLa cell malignant behaviors. Overall, we highlighted that USMB-miR-505 inhibited HeLa cell malignant behaviors by targeting AKT2.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Delizhaer Reheman ◽  
Jing Zhao ◽  
Shan Guan ◽  
Guan-Cheng Xu ◽  
Yi-Jie Li ◽  
...  

Abstract Pyrazolone complexes have strong anti-tumor and antibacterial properties, but the anti-tumor mechanism of pyrazolone-based copper complexes has not been fully understood. In this study, the possible mechanism and the inhibitory effect of a novel pyrazolone-based derivative compound [Cu(PMPP-SAL)(EtOH)] on human cervical cancer cells (HeLa cells) was investigated. [Cu(PMPP-SAL)(EtOH)] effectively inhibited proliferation of HeLa cells in vitro with an IC50 value of 2.082 after treatment for 72 h. Cell cycle analysis showed apoptosis was induced by blocking the cell cycle in the S phase. [Cu(PMPP-SAL)(EtOH)] promoted the loss of mitochondrial membrane potential, release of cytochrome c, PARP cleavage, and activation of caspase-3/9 in HeLa cells. Additionally, [Cu(PMPP-SAL)(EtOH)] inhibited the PI3K/AKT pathway and activated the P38/MAPK, and JNK/MAPK pathways. [Cu(PMPP-SAL)(EtOH)] also inhibited the phosphorylation of Iκ-Bα in the NF-κB pathway activated by TNF-α, thus restricting the proliferation of HeLa cells which were activated by TNF-α. In conclusion, [Cu(PMPP-SAL)(EtOH)] inhibited the growth of HeLa cells and induced apoptosis possibly via the caspase-dependent mitochondria-mediated pathway. These results suggest that [Cu(PMPP-SAL)(EtOH)] can be a potential candidate for the treatment of cervical cancer.


1988 ◽  
Vol 34 (3) ◽  
pp. 224-228 ◽  
Author(s):  
Aliza Kalo ◽  
Esther Segal

Findings from our previous studies revealed a correlation between the level of adherence in vitro of Candida albicans to human exfoliated vaginal epithelial cells (VEC) and the hormonal status of the cell donors. In the present study we investigated the effect of the sex hormones estradiol, estriol, progesterone, and testosterone on the binding of the yeasts to HeLa cell lines and VEC in vitro. Monolayers of HeLa cells were exposed to the hormones and yeasts under controlled conditions. The number of adherent yeasts per square millimetre of HeLa cell monolayers and the percentage of VEC with adherent yeasts was estimated by microscopic counts. The results showed that the tested sex hormones affected at various degrees the adhesion of yeasts to HeLa cells or VEC. Progesterone had the most marked effect, leading to a significant increase in the number of adherent yeasts to HeLa cells or in the percentage of adhesion of VEC. In addition, VEC were separated on Percoll gradients into the two cell types: superficial (S) and intermediate (I), cell types which appear physiologically under increased serum levels of estradiol or progesterone, respectively. Adhesion assays with the separated cell populations revealed an increased binding capacity of the I cells. The finding that progesterone increased the adherence of yeasts to genital mucosa and that VEC of the I type have a higher capacity to adhere the yeasts is compatible with our previous observation that increased numbers of I cells, appearing under high level of progesterone, are found in situations known to have predisposition to vaginal candidiasis. Thus, our data point to a possible involvement of the hormone progesterone in the adherence of C. albicans to genital epithelium.


2015 ◽  
Vol 12 (2) ◽  
pp. 55-59
Author(s):  
Edy Meiyanto

As chemotherapeutic backbone for breast cancer therapy, doxorubicin showed various side effects and induced resistancy of breast cancer cells. Development of targeted therapy on breast cancer focused on combinatorial therapy of doxorubicin and molecular targeted agents. PGV-0 and PGV-1, a curcumin analogue showed potency as co-chemotherapeutic agent with doxorubicin. Our previous study of PGV-0 and PGV-1 showed cytotoxic activity in T47D cells. Therefore, the aim of this research is to examine the synergistic effect of PGV-0, PGV-1 on the cytotoxic activity of doxorubicin through cell cycle modulation and apoptotic induction on MCF-7 breast cancer cell lines. The cytotoxic assay of PGV-0, PGV-1, doxorubicin, and their combination were carried out by using MTT assay. Cell cycle distribution and apoptosis were determined by flowcytometer FACS-Calibur and the flowcytometry data was analyzed using Cell Quest program. Single treatment of PGV-0, PGV-1 and doxorubicin showed cytotoxic effect on MCF-7 with cell viability IC50 value 50 µM, 6 µM and 350 nM respectively. Single treatment of Doxorubicin 175 nM induced G2/M arrest. Single treatment of PGV-0 5 µM induced G2/M arrest while in higher dose 12.5  µM, PGV-0 induced apoptosis. Combination of doxorubicin 175 nM and PGV-0 5 µM induced apoptosis. Combination of doxorubicin 175 nM and PGV-0 12.5 µM also increased apoptosis induction. Single treatment of PGV-1 0.6 µM induced G1 arrest while in higher dose 1.5  µM, PGV-1 induced apoptosis. Combination of doxorubicin 175 nM and PGV-1 0.6 µM induced apoptosis. Combination of doxorubicin 175 nM and PGV-0 1.5 µM also increased apoptosis induction. PGV-0 and PGV-1 are potential to be delevoped as co-chemotherapeutic agent for breast cancer by inducing apoptosis and cell cycle modulation, but the molecular mechanism need to be explored detail.  Key words: PGV-0, PGV-1, doxorubicin, co-chemotherapy, breast cancer, cell cycle arrest, apoptosis


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.


2021 ◽  
Author(s):  
saranya J ◽  
BS Sre ◽  
M Arivanandan ◽  
K Bhuvaneswari ◽  
S Sherin ◽  
...  

Abstract Using the ultrasonic approach, we produced a morphology involving cerium oxide/ Zinc oxide/graphene oxide (CeO2/ZnO/GO) nanocomposite-based system. The developed nanocomposite was examined using X-Ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and field emission scanning electron microscopy (FESEM). The average crystallite size was found to be 11.44 nm, as determined by XRD. FTIR analysis was used to confirm the existence of functional groups. FESEM was used to verify the morphological properties of CeO2/ZnO/GO. The micromorphology of CeO2/ZnO/GO nanocomposite reveals a smoother sheet-like structure. In addition, using an antiproliferative assay test, the developed nanosystem was evaluated for its scavenging anti-cancer capability against HeLa cell lines at various doses and incubation intervals. In our investigation, the effective IC50 concentration was reported to be 62.5 µg/ml at 72 h. Further, the developed nanosystem was evaluated for its killing efficacy against normal cell line. To identify apoptosis-associated alterations of cell membranes throughout the apoptosis process, a dual acridine orange/ethidium bromide (AO/EB) fluorescent staining was done using CeO2/ZnO/GO nanocomposite at three specific concentrations. The quantitative analysis was carried out using flow cytometry (FACS study) to determine the cell cycle during which the greatest number of HeLa cells were destroyed. According to the results of the FACS investigation, maximum cell cycle has taken place in P2, P4.As a result, the newly designed CeO2/ZnO/GO hybrid has demonstrated improved anti-cancer efficacy against the HeLa cell line, making it a better therapeutic agent for cervical cancer detection.


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.


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