scholarly journals The combination of berberine and methotrexate enhances anti-cancer effects in HeLa cancer cell line: A morphological study

2021 ◽  
Author(s):  
Hossein Majidzadeh ◽  
Mostafa Araj-Khodaei ◽  
Maryam Ghaffari ◽  
Amir Jafari ◽  
Dariush Shanehbandi ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Cancer Cells ◽  
Colorimetric Assay ◽  
Morphological Changes ◽  
Chemotherapeutic Agents ◽  
P Value ◽  
Combined System ◽  
Dna Ladder ◽  
Dapi Staining ◽  
Anti Cancer

Background: Co-administration of two or several either chemotherapeutic agents or conventional drugs as a combination treatment is the most effective method to increase therapeutic efficiency. Additive or synergistic influence are two mechanisms by which combination therapy causes a rise in optimal cancer therapy compared to a single treatment. Methods: Colorimetric assay was carried out to estimate the cytotoxicity of the combined system, followed by apoptosis assay to calculate the number of apoptotic cells. Both 4′,6-diamidino-2-phenylindole (DAPI) staining and DNA ladder were complemented tests to illuminate morphological changes and DNA fracturing on HeLa cancer cells. Statistical: Through Graph pad Prism 6.0 software. One-way ANOVA was used to determine the significance. A P-value of less than 0.05 was considered to be statistically significant. Results: In this study revealed that the combination of MTX and BER could inhibit the growth of HeLa cancer cells noticeably. Nevertheless, single BER and MTX were not as effective as a combined system to reduce cell viability at the same dose. Regarding the apoptosis induction and change in morphology of cancer cells’ nucleus, co-treatment of BER and MTX was more effective. The result was complemented with flow cytometry, DAPI staining and DNA ladder, which showed that BER+MTX depicted more anti-cancer effects. Conclusion: The combination therapy of HeLa cancer cells with BER and MTX showed high inhibition effect compared to other treated groups.

Natural-Derived Molecules as a Potential Adjuvant in Chemotherapy: Normal Cell Protectors and Cancer Cell Sensitizers

2021 ◽  
Vol 21 ◽  
Author(s):  
Rajib Hossain ◽  
Muhammad Torequl Islam ◽  
Mohammad S. Mubarak ◽  
Divya Jain ◽  
Rasel Khan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Side Effects ◽  
Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Polyphenolic Compounds ◽  
Anticancer Effect ◽  
Anticancer Activities ◽  
Normal Cells ◽  
Anti Cancer ◽  
Global Threat

Background: Cancer is a global threat to humans and a leading cause of death worldwide. Cancer treatment includes, among other things, the use of chemotherapeutic agents, compounds that are vital for treating and preventing cancer. However, chemotherapeutic agents produce oxidative stress along with other side effects that would affect the human body. Objective: To reduce the oxidative stress of chemotherapeutic agents in cancer and normal cells by naturally derived compounds with anti-cancer properties, and protect normal cells from the oxidation process. Therefore, the need to develop more potent chemotherapeutics with fewer side effects has become increasingly important. Method: Recent literature dealing with the antioxidant and anticancer activities of the naturally naturally-derived compounds: morin, myricetin, malvidin, naringin, eriodictyol, isovitexin, daidzein, naringenin, chrysin, and fisetin has been surveyed and examined in this review. For this, data were gathered from different search engines, including Google Scholar, ScienceDirect, PubMed, Scopus, Web of Science, Scopus, and Scifinder, among others. Additionally, several patient offices such as WIPO, CIPO, and USPTO were consulted to obtain published articles related to these compounds. Result: Numerous plants contain flavonoids and polyphenolic compounds such as morin, myricetin, malvidin, naringin, eriodictyol, isovitexin, daidzein, naringenin, chrysin, and fisetin, which exhibit ‎antioxidant, anti-inflammatory, and anti-carcinogenic actions via several mechanisms. These compounds show sensitizers of cancer cells and protectors of healthy cells. Moreover, these compounds can reduce oxidative stress, which is accelerated by chemotherapeutics and exhibit a potent anticancer effect on cancer cells. Conclusions: Based on these findings, more research is recommended to explore and evaluate such flavonoids and polyphenolic compounds.

scholarly journals RHAMM-target peptides inhibit invasion of breast cancer cells

2017 ◽  
Vol 1 (2) ◽  
pp. 138-148 ◽  
Author(s):  
Natalia Akentieva
Keyword(s):  
Breast Cancer ◽  
Confocal Microscopy ◽  
Cancer Cells ◽  
Mitotic Spindle ◽  
Breast Cancer Cells ◽  
Morphological Changes ◽  
Therapeutic Activity ◽  
Multiple Functions ◽  
Anti Cancer

Abstract RHAMM is hyaluronan- receptor with multiple functions in the cell, RHAMM is involved in proliferation, motility, migration, invasion, mitotic spindle formation in tumour cells. Therefore, RHAMM could be a relevant target for molecular targeted therapies against tumors.The role of RHAMM-target peptides in inhibition invasion for preventing breast cancer has not yet been investigated. Base on this, we analyzed the RHAMM-target peptides for their therapeutic activity against breast cancer cells. In the present study, we examined the effect of RHAMM-target peptides on the invasion of breast cancer cells (MDAMB- 231), using confocal microscopy. We shown that RHAMM-target peptides decreased formation of invadopodia of breast cancer cells. The treatment of breast cancer cells by RHAMM -target peptides inhibited the invasion up to 99 %. Additionally, RHAMM-target peptides induced the morphological changes of of breast cancer cells. Therefore, based on these results, we can conclude that RHAMM-target peptides may be potential anti-cancer agents.

scholarly journals MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 29 ◽  
Author(s):  
Hyun Ah Seo ◽  
Sokviseth Moeng ◽  
Seokmin Sim ◽  
Hyo Jeong Kuh ◽  
Soo Young Choi ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Therapeutic Resistance ◽  
Cancer Therapies ◽  
Anti Cancer ◽  
Different Types ◽  
Therapeutic Responses

The susceptibility of cancer cells to different types of treatments can be restricted by intrinsic and acquired therapeutic resistance, leading to the failure of cancer regression and remission. To overcome this problem, a combination therapy has been proposed as a fundamental strategy to improve therapeutic responses; however, resistance is still unavoidable. MicroRNA (miRNAs) are associated with cancer therapeutic resistance. The modulation of dysregulated miRNA levels through miRNA-based therapy comprising a replacement or inhibition approach has been proposed to sensitize cancer cells to other anti-cancer therapies. The combination of miRNA-based therapy with other anti-cancer therapies (miRNA-based combinatorial cancer therapy) is attractive, due to the ability of miRNAs to target multiple genes associated with the signaling pathways controlling therapeutic resistance. In this article, we present an overview of recent findings on the role of therapeutic resistance-related miRNAs in different types of cancer. We review the feasibility of utilizing dysregulated miRNAs in cancer cells and extracellular vesicles as potential candidates for miRNA-based combinatorial cancer therapy. We also discuss innate properties of miRNAs that need to be considered for more effective combinatorial cancer therapy.

Ab Initio Studies of Anti-Cancer Drugs

1998 ◽  
Author(s):  
Anne-Marie Sapse
Keyword(s):  
Cancer Therapy ◽  
Ab Initio ◽  
Cancer Cells ◽  
Alkylating Agents ◽  
Experimental Studies ◽  
Chemotherapeutic Agents ◽  
Theoretical Studies ◽  
Cancer Drugs ◽  
Normal Cells ◽  
Anti Cancer

Cancer is an extraordinarily complicated group of diseases which are characterized by the loss of normal control of the maintenance of cellular organization in the tissues. It is still not completely understood how much of the disease is of genetic, viral, or environmental origin. The result, however, is that cancer cells possess growth advantages over normal cells, a reality which damages the host by local pressure effects, destruction of tissues, and secondary systemic effects. As such, a goal of cancer therapy is the destruction of cancer cells via chemotherapeutic agents or radiation. Since the late 1940s, when Farber treated leukemia with methotrexate, cancer therapy with cytotoxic drugs made enormous progress. Chemotherapy is usually integrated with other treatments such as surgery, radiotherapy, and immunotherapy, and it is clear that post-surgery, it is effective with solid tumors. This is due to the fact that only systemic therapy can attack micrometastases. The rationale for using chemotherapy is the control of tumor-cell populations via a killing mechanism. The major problem in this approach is the lack of selectivity of chemotherapeutic agents. Some agents indeed preferentially kill cancer cells, but no agents have been synthesized yet which kill only cancer cells and do not affect normal cells. Unfortunately, normal tissues are affected, giving rise to a multitude of side effects. In addition to drugs exhibiting cytotoxic activity, antiproliferative drugs are also formulated. According to their mode of action, anti-cancer drugs are divided into several classes. . . . alkylating agents antimetabolites DNA intercalators mitotic inhibitors lexitropsins drugs which bind covalently to DNA . . . Experimental studies of these molecules are complemented and enhanced by theoretical studies. Some of the theoretical studies use molecular mechanics methods while others apply ab initio or semi-empirical quantum-chemistry methods. Most of these molecules are large and besides their structures and properties it is important to investigate their interaction with DNA fragments (themselves large molecules). Ab initio calculations cannot always be applied to the whole system. Therefore, models are used and through a judicious choice of the entities investigated, the calculations can shed light on the problem and provide enough information to complement the experimental studies.

Immune System Activation After Cisplatin or “Poly-Plat” Treatment: An in Vivo Study

1998 ◽  
Vol 4 (S2) ◽  
pp. 1048-1049
Author(s):  
D. J. Telgen ◽  
S. K. Aggarwal
Keyword(s):  
Sodium Chloride ◽  
Peripheral Blood ◽  
Chemotherapeutic Agent ◽  
Morphological Changes ◽  
Chemotherapeutic Agents ◽  
Immune System Activation ◽  
Anti Cancer ◽  
System Activation ◽  
Cancer Agent

Cisplatin (cw-diamminedichloroplatinum II; CDDP) is a broad spectrum anti-cancer agent with severe toxic side effects. New platinum based chemotherapeutic agents with similar properties are in constant development. Poly-plat (Poly-[(teans-l,2-diaminocyclohexane) platinum]-carboxyamylose), a novel second generation platinum chemotherapeutic agent, has been shown to be less toxic compared to CDDP. The purpose of this paper was to examine the morphological changes in the Kupffer cells in the liver after poly-plat treatment in rats and compare the results obtained after CDDP. Peripheral blood was also examined for levels of circulating leukocytes.Wistar rats (120-160 g) were given intraperitoneal injections of either CDDP (9 mg/kg in 0.9% sodium chloride) or poly-plat (10 mg/kg in 0.9% sodium chloride) over a five day period. Controls were treated with equal amounts of the vehicle of injection. Peripheral blood was collected via tail vein beginning 1 day prior to treatment and continuing 10 days after treatment.

scholarly journals Photodynamic Therapy and Hyperthermia in Combination Treatment—Neglected Forces in the Fight against Cancer

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1147
Author(s):  
Aleksandra Bienia ◽  
Olga Wiecheć-Cudak ◽  
Aleksandra Anna Murzyn ◽  
Martyna Krzykawska-Serda
Keyword(s):  
Photodynamic Therapy ◽  
Combination Therapy ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Combination Treatment ◽  
Therapeutic Agent ◽  
Diagnostic Methods ◽  
Cancer Therapies ◽  
Treatment Side Effects ◽  
Anti Cancer

Cancer is one of the leading causes of death in humans. Despite the progress in cancer treatment, and an increase in the effectiveness of diagnostic methods, cancer is still highly lethal and very difficult to treat in many cases. Combination therapy, in the context of cancer treatment, seems to be a promising option that may allow minimizing treatment side effects and may have a significant impact on the cure. It may also increase the effectiveness of anti-cancer therapies. Moreover, combination treatment can significantly increase delivery of drugs to cancerous tissues. Photodynamic therapy and hyperthermia seem to be ideal examples that prove the effectiveness of combination therapy. These two kinds of therapy can kill cancer cells through different mechanisms and activate various signaling pathways. Both PDT and hyperthermia play significant roles in the perfusion of a tumor and the network of blood vessels wrapped around it. The main goal of combination therapy is to combine separate mechanisms of action that will make cancer cells more sensitive to a given therapeutic agent. Such an approach in treatment may contribute toward increasing its effectiveness, optimizing the cancer treatment process in the future.

scholarly journals Chemoprotective and chemosensitizing effects of apigenin on cancer therapy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zahra Nozhat ◽  
Shabnam Heydarzadeh ◽  
Zahra Memariani ◽  
Amirhossein Ahmadi
Keyword(s):  
Drug Resistance ◽  
Clinical Trials ◽  
Side Effects ◽  
Combination Therapy ◽  
Molecular Mechanisms ◽  
Cancer Therapeutics ◽  
Therapeutic Index ◽  
Chemotherapeutic Agents ◽  
Potential Candidate ◽  
Anti Cancer

Abstract Background Therapeutic resistance to radiation and chemotherapy is one of the major obstacles in cancer treatment. Although synthetic radiosensitizers are pragmatic solution to enhance tumor sensitivity, they pose concerns of toxicity and non-specificity. In the last decades, scientists scrutinized novel plant-derived radiosensitizers and chemosensitizers, such as flavones, owing to their substantial physiological effects like low toxicity and non-mutagenic properties on the human cells. The combination therapy with apigenin is potential candidate in cancer therapeutics. This review explicates the combinatorial strategies involving apigenin to overcome drug resistance and boost the anti-cancer properties. Methods We selected full-text English papers on international databases like PubMed, Web of Science, Google Scholar, Scopus, and ScienceDirect from 1972 up to 2020. The keywords included in the search were: Apigenin, Chemoprotective, Chemosensitizing, Side Effects, and Molecular Mechanisms. Results In this review, we focused on combination therapy, particularly with apigenin augmenting the anti-cancer effects of chemo drugs on tumor cells, reduce their side effects, subdue drug resistance, and protect healthy cells. The reviewed research data implies that these co-therapies exhibited a synergistic effect on various cancer cells, where apigenin sensitized the chemo drug through different pathways including a significant reduction in overexpressed genes, AKT phosphorylation, NFκB, inhibition of Nrf2, overexpression of caspases, up-regulation of p53 and MAPK, compared to the monotherapies. Meanwhile, contrary to the chemo drugs alone, combined treatments significantly induced apoptosis in the treated cells. Conclusion Briefly, our analysis proposed that the combination therapies with apigenin could suppress the unwanted toxicity of chemotherapeutic agents. It is believed that these expedient results may pave the path for the development of drugs with a high therapeutic index. Nevertheless, human clinical trials are a prerequisite to consider the potential use of apigenin in the prevention and treatment of various cancers. Conclusively, the clinical trials to comprehend the role of apigenin as a chemoprotective agent are still in infancy. Graphical Abstract

scholarly journals Effect of the Cellular Extract of Co-cultured Lactobacillus Casei on BAX and Human β-Defensin 2 Genes Expression in HT29 Cells

2020 ◽  
Vol 26 (4) ◽  
pp. 364-381
Author(s):  
Mina Yavari ◽  
◽  
Changiz Ahmadizadeh ◽  
Keyword(s):  
Cancer Cells ◽  
Cell Line ◽  
Lactobacillus Casei ◽  
Ht29 Cell ◽  
Resistant Bacteria ◽  
Dna Ladder ◽  
Dapi Staining ◽  
Ht29 Cells ◽  
Cellular Extract ◽  
Ht29 Cell Line

Aims: Defensins are cysteine-rich antimicrobial cationic peptides and BAX is a proapoptotic gene that can cause cell death. This study aimed to investigate the effect of cellular extract of co-cultured Lactobacillus casei on the expression of BAX and human β-defensin 2 (hBD-2) genes in HT29 cells. Methods & Materials: This experimental study was conducted in the Research Center for Pharmaceutical Nanotechnology of Tabriz University of Medical Sciences in 2017. The HT29 cell line was obtained from the Pasteur Institute of Iran, and cells were assessed using Microculture Tetrazolium Test (MTT) after culturing. DNA was extracted from the treated cells, and then the DNA ladder assay was carried out. After preparing cDNA, the expression levels of BAX and hBD-2 genes in the HT29 cell line were measured using a real-time Polymerase Chain Reaction (PCR) method. Findings: The results of the MTT assay indicated that Lactobacillus casei inhibited the proliferation of HT29 cells and induced apoptosis in these cells. Results of DAPI staining and DNA ladder assay obtained from treating HT29 cells by Lactobacillus casei showed qualitative changes in cell apoptosis. Moreover, realtime PCR results indicated that Lactobacillus casei bacteria significantly increased the expression of the hBD-2 gene in HT29 colon cancer cells within 12-24 hours (P= 0.023), while BAX gene expression showed no significant change in the first 24 hours (P= 0.37). Conclusion: The extract of Lactobacillus casei can be used to stimulate cancer cells to produce β-defensins, inhibit pathogens, prevent the stimulation of cellular signaling, and fight antibiotic-resistant bacteria.

scholarly journals Hepatocellular Toxicity of Paris Saponins I, II, VI and VII on Two Kinds of Hepatocytes-HL-7702 and HepaRG Cells, and the Underlying Mechanisms

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 690 ◽  
Author(s):  
Wenping Wang ◽  
Yi Liu ◽  
Mingyi Sun ◽  
Na Sai ◽  
Longtai You ◽  
...  
Keyword(s):  
Morphological Changes ◽  
P53 Protein ◽  
Death Receptor ◽  
Dependent Manner ◽  
Dapi Staining ◽  
Heparg Cells ◽  
Anti Cancer ◽  
Underlying Mechanisms ◽  
Induced Apoptosis ◽  
Induced Changes

Rhizoma paridis is a popularly-used Chinese medicine in clinics, based on the pharmacodynamic properties of its saponin components. The four main saponins in Rhizoma paridis are designated saponins I, II, VI, and VII. At present, much attention is focused on the anticancer effect of Rhizoma paridis which is manifested in its cytotoxicity to various cancer cells. The purpose of this study was to investigate the hepatocellular toxicities of the four saponins in Rhizoma paridis and the relative intensities of their cytotoxic effects. It was found that the four saponins were cytotoxic to two types of hepatocytes-HL-7702 and HepaRG cells. The cytotoxicities of the four saponins to the two cell models were compared. One of the most cytotoxic saponins was Rhizoma paridis saponin I (PSI). This was used to determine the mechanism of hepatocellular toxicity. Results from MTT assays demonstrated that the four saponins induced apoptosis of the two hepatocyte models in a dose-dependent and time-dependent manner. In addition, fluorescent 4′,6-diamidino-2-phenylindole (DAPI) staining was used to observe the morphological changes of HepaRG cells after saponin administration. Further, as the concentration increased, PSI-induced lactate dehydrogenase (LDH) release from HepaRG cells increased gradually. In addition, PSI enhanced the levels of reactive oxygen species (ROS) and blocked the S and G2 phases of the cell cycle in HepaRG cells. A western blot indicated that PSI upregulated the protein expression levels of p53, p21, and Fas. Furthermore, the PSI-induced changes in the p53 protein increased the Bax/bcl-2 ratio, resulting in enhancement of the release of mitochondrial cytochrome c, activation of caspases-3, -8, and -9, poly-ADP ribose polymerase (PARP), and ultimately apoptosis. Increased Fas protein activated caspase-8, which led to the activation of caspase-3 and its downstream PARP protein, resulting in cell apoptosis. These results indicate that PSI induced apoptosis in HepaRG cells through activation of ROS and death receptor pathways. The results obtained in this study suggest that the hepatocellular toxicity of saponins in Rhizoma paridis should be considered during the clinical application of this drug. In addition, they provide a reference for future anti-cancer studies on Rhizoma paridis.

scholarly journals Combination of glucose transporter inhibitors and oestrone analogues on breast cancer cells

2014 ◽  
Vol 33 (1) ◽  
Author(s):  
A. Van Tonder ◽  
A.J. Joubert ◽  
A.D. Cromarty
Keyword(s):  
Breast Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Clinical Setting ◽  
Breast Cancer Cells ◽  
Glucose Transporter ◽  
Molecular Subtypes ◽  
Chemotherapeutic Agents ◽  
Reduced Toxicity ◽  
Synergistic Combinations

Combinations of chemotherapeutic agents are commonly used in the clinical setting as this allows for a reduction in the dose of each agent, and thus reduced toxicity, with increased therapeutic efficacy. This study proved the feasibility of synergy between two novel oestrone analogues and GLUT inhibitors. The synergistic combinations which have been identified indicate that the different molecular subtypes of breast cancer, as represented by the cell lines used, respond differently to the combination therapy. These differences will be further investigated.

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