The p53-mediated sensitivity of cancer cells to chemotherapeutic agents is conditioned by the status of the retinoblastoma protein

PRDM14 belongs to the PR domain-containing (PRDM) family. Although a precise understanding focused on the function of PRDM14 to maintain stemness and pluripotency in embryonic stem cells via epigenetic mechanisms, growing experimental evidence has been linked PRDM14 to human cancers. In adults, PRDM14 has low expression in human tissues. Aberrant PRDM14 expression is connected with various malignant histological types and solid cancers, where PRDM14 can act as a driver of oncogenic processes. Overexpression of RPDM14 enhanced cancer cells growth and reduced cancer cells sensitive to chemotherapeutic agents. Reducing the expression of PRDM14 in cancer cells can enhance the therapeutic sensitivity of drugs to cancer cells, suggesting that aberrant PRDM14 may have a carcinogenic characteristic in tumor therapy and as a new molecular target. This review summarizes the structure and oncogenic properties of PRDM14 in different malignancies and suggests that PRDM14 may be a potential therapeutic molecular target for tumor treatment.

Emodin Enhances the Chemosensitivity of Endometrial Cancer by Inhibiting ROS-Mediated Cisplatin-resistance

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666171219113036 ◽

2018 ◽

Vol 18 (7) ◽

pp. 1054-1063 ◽

Cited By ~ 4

Author(s):

Ning Ding ◽

Hong Zhang ◽

Shan Su ◽

Yumei Ding ◽

Xiaohui Yu ◽

...

Keyword(s):

Drug Resistance ◽

Endometrial Cancer ◽

Cancer Cells ◽

Chemotherapeutic Agent ◽

Annexin V ◽

Chemotherapeutic Agents ◽

Endometrial Cancer Cell ◽

Animal Survival ◽

Apoptosis Level

Background: Endometrial cancer is a common cause of death in gynecological malignancies. Cisplatin is a clinically chemotherapeutic agent. However, drug-resistance is the primary cause of treatment failure. Objective: Emodin is commonly used clinically to increase the sensitivity of chemotherapeutic agents, yet whether Emodin promotes the role of Cisplatin in the treatment of endometrial cancer has not been studied. Method: CCK-8 kit was utilized to determine the growth of two endometrial cancer cell lines, Ishikawa and HEC-IB. The apoptosis level of Ishikawa and HEC-IB cells was detected by Annexin V / propidium iodide double-staining assay. ROS level was detected by DCFH-DA and NADPH oxidase expression. Expressions of drug-resistant genes were examined by real-time PCR and Western blotting. Results: Emodin combined with Cisplatin reduced cell growth and increased the apoptosis of endometrial cancer cells. Co-treatment of Emodin and Cisplatin increased chemosensitivity by inhibiting the expression of drugresistant genes through reducing the ROS levels in endometrial cancer cells. In an endometrial cancer xenograft murine model, the tumor size was reduced and animal survival time was increased by co-treatment of Emodin and Cisplatin. Conclusion: This study demonstrates that Emodin enhances the chemosensitivity of Cisplatin on endometrial cancer by inhibiting ROS-mediated expression of drug-resistance genes.

A Novel Synthetic Compound (E)-5-((4-oxo-4H-chromen-3-yl)methyleneamino)-1-phenyl-1H-pyrazole-4-carbonitrile Inhibits TNFα-Induced MMP9 Expression via EGR-1 Downregulation in MDA-MB-231 Human Breast Cancer Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21145080 ◽

2020 ◽

Vol 21 (14) ◽

pp. 5080

Author(s):

Munki Jeong ◽

Euitaek Jung ◽

Young Han Lee ◽

Jeong Kon Seo ◽

Seunghyun Ahn ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Chemotherapeutic Agents ◽

Synthetic Compound ◽

Necrosis Factor Alpha ◽

Mmp9 Expression ◽

Extracellular Signal ◽

Signaling Axis ◽

Early Growth Response 1

Breast cancer is a common malignancy among women worldwide. Gelatinases such as matrix metallopeptidase 2 (MMP2) and MMP9 play crucial roles in cancer cell migration, invasion, and metastasis. To develop a novel platform compound, we synthesized a flavonoid derivative, (E)-5-((4-oxo-4H-chromen-3-yl)methyleneamino)-1-phenyl-1H-pyrazole-4-carbonitrile (named DK4023) and characterized its inhibitory effects on the motility and MMP2 and MMP9 expression of highly metastatic MDA-MB-231 breast cancer cells. We found that DK4023 inhibited tumor necrosis factor alpha (TNFα)-induced motility and F-actin formation of MDA-MB-231 cells. DK4023 also suppressed the TNFα-induced mRNA expression of MMP9 through the downregulation of the TNFα-extracellular signal-regulated kinase (ERK)/early growth response 1 (EGR-1) signaling axis. These results suggest that DK4023 could serve as a potential platform compound for the development of novel chemopreventive/chemotherapeutic agents against invasive breast cancer.

Melatonin as an Adjuvant to Antiangiogenic Cancer Treatments

Cancers ◽

10.3390/cancers13133263 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3263

Author(s):

Alicia González ◽

Carolina Alonso-González ◽

Alicia González-González ◽

Javier Menéndez-Menéndez ◽

Samuel Cos ◽

...

Keyword(s):

Synergistic Effect ◽

Protective Effect ◽

Cancer Cells ◽

Tumor Cells ◽

Chemotherapeutic Agents ◽

Inhibitory Effects ◽

Anticancer Effect ◽

Cancer Treatments ◽

Melatonin Administration ◽

Effects Of Radiation

Melatonin is a hormone with different functions, antitumor actions being one of the most studied. Among its antitumor mechanisms is its ability to inhibit angiogenesis. Melatonin shows antiangiogenic effects in several types of tumors. Combination of melatonin and chemotherapeutic agents have a synergistic effect inhibiting angiogenesis. One of the undesirable effects of chemotherapy is the induction of pro-angiogenic factors, whilst the addition of melatonin is able to overcome these undesirable effects. This protective effect of the pineal hormone against angiogenesis might be one of the mechanisms underlying its anticancer effect, explaining, at least in part, why melatonin administration increases the sensitivity of tumors to the inhibitory effects exerted by ordinary chemotherapeutic agents. Melatonin has the ability to turn cancer totally resistant to chemotherapeutic agents into a more sensitive chemotherapy state. Definitely, melatonin regulates the expression and/or activity of many factors involved in angiogenesis which levels are affected (either positively or negatively) by chemotherapeutic agents. In addition, the pineal hormone has been proposed as a radiosensitizer, increasing the oncostatic effects of radiation on tumor cells. This review serves as a synopsis of the interaction between melatonin and angiogenesis, and we will outline some antiangiogenic mechanisms through which melatonin sensitizes cancer cells to treatments, such as radiotherapy or chemotherapy.

Links between Inflammation and Postoperative Cancer Recurrence

Journal of Clinical Medicine ◽

10.3390/jcm10020228 ◽

2021 ◽

Vol 10 (2) ◽

pp. 228

Author(s):

Tomonari Kinoshita ◽

Taichiro Goto

Keyword(s):

Clinical Practice ◽

Cancer Cells ◽

Cancer Recurrence ◽

Complete Resection ◽

The Body ◽

Cancer Development ◽

Clinical Settings ◽

Cancer Type ◽

Clinical Indicators ◽

The Status

Despite complete resection, cancer recurrence frequently occurs in clinical practice. This indicates that cancer cells had already metastasized from their organ of origin at the time of resection or had circulated throughout the body via the lymphatic and vascular systems. To obtain this potential for metastasis, cancer cells must undergo essential and intrinsic processes that are supported by the tumor microenvironment. Cancer-associated inflammation may be engaged in cancer development, progression, and metastasis. Despite numerous reports detailing the interplays between cancer and its microenvironment via the inflammatory network, the status of cancer-associated inflammation remains difficult to recognize in clinical settings. In the current paper, we reviewed clinical reports on the relevance between inflammation and cancer recurrence after surgical resection, focusing on inflammatory indicators and cancer recurrence predictors according to cancer type and clinical indicators.

Cre-loxP-mediated bax gene activation reduces growth rate and increases sensitivity to chemotherapeutic agents in human gastric cancer cells

Cancer Gene Therapy ◽

10.1038/sj.cgt.7700181 ◽

2000 ◽

Vol 7 (6) ◽

pp. 885-892 ◽

Cited By ~ 11

Author(s):

Koga Komatsu ◽

Susumu Suzuki ◽

Tooru Shimosegawa ◽

Jun-ichi Miyazaki ◽

Takayoshi Toyota

Keyword(s):

Gastric Cancer ◽

Growth Rate ◽

Cancer Cells ◽

Gene Activation ◽

Chemotherapeutic Agents ◽

Human Gastric Cancer ◽

Gastric Cancer Cells ◽

Bax Gene

A novel radiolytic rotenone derivative, rotenoisin A, displays potent anticarcinogenic activity in breast cancer cells

Journal of Radiation Research ◽

10.1093/jrr/rrab005 ◽

2021 ◽

Author(s):

Dong-ho Bak ◽

Seong Hee Kang ◽

Chul-hong Park ◽

Byung Yeoup Chung ◽

Hyoung-Woo Bai

Keyword(s):

Breast Cancer ◽

Adverse Effects ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Parent Compound ◽

Inhibitory Effect ◽

Chemotherapeutic Agents ◽

Epidermal Keratinocytes ◽

Functional Changes ◽

Structural Modifications

Abstract Chemotherapy for cancer treatment has therapeutic limitations, such as drug resistance, excessive toxic effects and undesirable adverse effects. Therefore, efforts to improve the safety and efficacy of chemotherapeutic agents are essential. Ionizing radiation can improve physiological and pharmacological properties by transforming structural modifications of the drug. In this study, in order to reduce the adverse effects of rotenone and increase anticancer activity, a new radiolytic rotenone derivative called rotenoisin A was generated through radiolytic transformation. Our findings showed that rotenoisin A inhibited the proliferation of breast cancer cells and increased the rate of apoptosis, whereas it had no inhibitory effect on primary epidermal keratinocytes compared with rotenone. Moreover, rotenoisin A-induced DNA damage by increasing reactive oxygen species (ROS) accumulation. It was also confirmed not only to alter the composition ratio of mitochondrial proteins, but also to result in structural and functional changes. The anticancer effect and molecular signalling mechanisms of rotenoisin A were consistent with those of rotenone, as previously reported. Our study suggests that radiolytic transformation of highly toxic compounds may be an alternative strategy for maintaining anticancer effects and reducing the toxicity of the parent compound.

Dasatinib (BMS-35482) Interacts Synergistically With Docetaxel, Gemcitabine, Topotecan, and Doxorubicin in Ovarian Cancer Cells With High SRC Pathway Activation and Protein Expression

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000056 ◽

2014 ◽

Vol 24 (2) ◽

pp. 218-225 ◽

Cited By ~ 5

Author(s):

Angeles Alvarez Secord ◽

Deanna Teoh ◽

Jingquan Jia ◽

Andrew B. Nixon ◽

Lisa Grace ◽

...

Keyword(s):

Ovarian Cancer ◽

Protein Expression ◽

Cancer Cells ◽

Combination Index ◽

Chemotherapeutic Agents ◽

Cytotoxic Agents ◽

Ovarian Cancer Cells ◽

Response Curves ◽

Pathway Activation ◽

Skov3 Cells

PurposeThis study aimed to explore the activity of dasatinib in combination with docetaxel, gemcitabine, topotecan, and doxorubicin in ovarian cancer cells.MethodsCells with previously determined SRC pathway and protein expression (SRC pathway/SRC protein IGROV1, both high; SKOV3, both low) were treated with dasatinib in combination with the cytotoxic agents. SRC and paxillin protein expression were determined pretreatment and posttreatment. Dose-response curves were constructed, and the combination index (CI) for drug interaction was calculated.ResultsIn the IGROV1 cells, dasatinib alone reduced phospho-SRC/total SRC 71% and p-paxillin/t-paxillin ratios 77%. Phospho-SRC (3%–33%; P = 0.002 to 0.04) and p-paxicillin (6%–19%; P = 0.01 to 0.05) levels were significantly reduced with dasatinib in combination with each cytotoxic agent. The combination of dasatinib and docetaxel, gemcitabine, or topotecan had a synergistic antiproliferative effect (CI, 0.49–0.68), whereas dasatinib combined with doxorubicin had an additive effect (CI, 1.08).In SKOV3 cells, dasatinib resulted in less pronounced reductions of phospho-SRC/total SRC (49%) and p-paxillin/t-paxillin (62%). Phospho-SRC (18%; P < 0.001) and p-paxillin levels (18%; P = 0.001; 9%; P = 0.007) were significantly decreased when dasatinib was combined with docetaxel and topotecan (p-paxillin only). Furthermore, dasatinib combined with the cytotoxics in the SKOV3 cells produced an antagonistic interaction on the proliferation of these cells (CI, 1.49–2.27).ConclusionsDasatinib in combination with relapse chemotherapeutic agents seems to interact in a synergistic or additive manner in cells with high SRC pathway activation and protein expression. Further evaluation of dasatinib in combination with chemotherapy in ovarian cancer animal models and exploration of the use of biomarkers to direct therapy are warranted.