scholarly journals Verteporfin can Reverse the Paclitaxel Resistance Induced by YAP Over-Expression in HCT-8/T Cells without Photoactivation through Inhibiting YAP Expression

2016 ◽  
Vol 39 (2) ◽  
pp. 481-490 ◽  
Author(s):  
Wang Pan ◽  
Qian Wang ◽  
Yi Zhang ◽  
Naishu Zhang ◽  
Jiamin Qin ◽  
...  
Keyword(s):  
T Cells ◽  
Combination Therapy ◽  
Multiple Drug Resistance ◽  
Protein Detection ◽  
Multiple Drug ◽  
Over Expression ◽  
Anti Cancer ◽  
The Relationship ◽  
Proliferation And Invasion ◽  
Main Factor

Background/Aims: Paclitaxel (PTX) is one of the most effective anti-cancer drugs. However, multiple drug resistance is still the main factor that hinders the effective treatment of cancer with PTX. Several factors including YAP over-expression can cause PTX resistance. In this study, we aimed to verify the role YAP plays in PTX resistance, explore the reversal of PTX resistance by verteporfin (VP) and investigate the effect of combination therapy of PTX and VP on the PTX resistant colon cancer cells (HCT-8/T). Methods: To study the relationship between YAP and PTX resistance, a stable YAP-over-expression or YAP silencing cell line was generated by transfected with YAP-plasmids or siYAP-RNA. WST-1 assay was performed to detect the cytotoxicity of PTX on HCT-8 and HCT-8/T cells. Clone formation assay and Transwell assay was preformed to determine the cell proliferation and invasion ability respectively. Immunofluorescence and Western blot analysis was performed for protein detection. Results: YAP was stronger expressed in HCT-8/T than in HCT-8, and PTX resistance was positively correlated with the level of YAP expression. VP, a strongly YAP inhibitor, could reduce the PTX resistance on HCT-8/T cells without light activation by inhibiting YAP. Beside, VP and PTX combination therapy showed synergism on inhibition of YAP and cytotoxicity to HCT-8/T. Moreover, verteporfin and PTX combination therapy affect the invasion and colony formation ability and induce apoptosis of HCT-8/T cells. Conclusions: VP can reverse the PTX resistance induced by YAP over-expression in HCT-8/T cells without photoactivation through inhibiting YAP expression.

Canine mammary carcinoma cell line are resistant to chemosensitizers: verapamil and cyclosporin A

2014 ◽  
Vol 17 (1) ◽  
pp. 9-17 ◽  
Author(s):  
M. Król ◽  
K.M. Pawłowski ◽  
K. Majchrzak ◽  
J. Mucha ◽  
T. Motyl
Keyword(s):  
Cyclosporin A ◽  
Cell Lines ◽  
Lung Metastases ◽  
Multiple Drug Resistance ◽  
Clinical Problem ◽  
Multiple Drug ◽  
Glycoprotein P ◽  
Membrane Pump ◽  
Over Expression ◽  
Cancer Chemoresistance

Abstract Cancer chemotherapy can fail in many ways. One of the most significant is the development of multiple drug resistance (MDR), which constitutes a serious clinical problem. The development of MDR relates to the expression of a major membrane pump, P-glycoprotein (P-gp). Thus, currently one of the goals of experimental and clinical oncology is to decrease its activity. So far, many different P-gp inhibitors are available, but their efficacy is still questionable and requires further study. The aim of our study was to assess an impact of classical P-gp inhibitors (verapamil and cyclosporin A) in the reversion of multidrug resistance in canine mammary cancer cells. We used two cell lines isolated from mammary tumors and two cell lines isolated from their lung metastases. All of them showed P-gp over-expression confirmed using Real-time rt-PCR, Skan^R screening station and confocal microscopy. The FACS analysis showed that in three of the examined cell lines, treatment with verpamil/cyclosporin A was ineffective to reverse cancer chemoresistance. However, more studies in this field are required.

scholarly journals 3,3′-Diindolylmethane Promotes Gastric Cancer Progression via β-TrCP-Mediated NF-κB Activation in Gastric Cancer-Derived MSCs

2021 ◽  
Vol 11 ◽  
Author(s):  
Hui Shi ◽  
Yaoxiang Sun ◽  
Hongru Ruan ◽  
Cheng Ji ◽  
Jiahui Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Multiple Drug Resistance ◽  
Cancer Drug ◽  
Multiple Drug ◽  
High Morbidity ◽  
Related Factors ◽  
Anti Cancer

Gastric cancer is a malignant tumor characterized by high morbidity and invasion. Surgery combined with chemo-radiotherapy is the most common treatment for gastric cancer, while multiple drug resistance always results in treatment failure. Once the anti-tumor drugs enter the tumor foci, tumor cells as well as those found in the microenvironment are affected. However, the effects of drugs on tumor microenvironment (TME) are easily overlooked. In this study, we investigated the effects of the anti-cancer drug 3,3’-diindolylmethane (DIM) on gastric cancer-derived mesenchymal stem cells (GC-MSCs) and their subsequent impact on cancer progression. Surprisingly, we found that the therapeutic concentration of DIM upregulated the expression level of tumor-related factors such as CCL-2, IL-6, and IL-8 in GC-MSCs. The conditioned medium of DIM-treated GC-MSCs promoted the proliferation, invasion, and migration of gastric cancer cells in vitro and tumor growth in vivo. Mechanistically, DIM enhanced the expression of β-TrCP, an E3 ubiquitin ligase leading to IκBα degradation and NF-κB activation in GC-MSCs. The β-TrCP knockdown partially eliminated positive results caused by DIM. Our results showed that the therapeutic dosage of DIM induced cell death in cancer cells, while enhancing MSC paracrine functions in the stroma to offset the original DIM effect on cancer cells. These findings provide a new mechanism of anti-cancer drug resistance and remind us to adjust the chemotherapeutic scheme by combining the anti-cancer drug with an appropriate signaling pathway inhibitor to block the side effects of drug on targeted TME cells.

Recent Development in Indole Derivatives as Anticancer Agent: A Mechanistic Approach

2021 ◽  
Vol 21 ◽  
Author(s):  
Neha Devi ◽  
Kamalpreet Kaur ◽  
Avadh Biharee ◽  
Vikas Jaitak
Keyword(s):  
Estrogen Receptor ◽  
Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Multiple Drug Resistance ◽  
Mtor Pathway ◽  
Multiple Drug ◽  
Significant Activity ◽  
Indole Derivatives ◽  
Tubulin Inhibitor ◽  
Anti Cancer

Background: Cancer accounts for several deaths each year. There are multiple FDA approved drugs for cancer treatments. Due to the severe side effects and multiple drug resistance, the current drug therapies become ineffective. So, the newer moieties with fewer toxic effects are necessary for the development. Objective: The mechanism of indole derivatives as anti-cancer agents with their major target is explored in detail in this article. Methods: Recent advances and mechanism of indole derivatives as anti-cancer agents are reviewed. This review suggests a detailed explanation of multiple mechanisms of action of various indole derivatives: cell cycle arrest, aromatase inhibitor estrogen receptor regulator, tubulin inhibitor, a tyrosine kinase inhibitor, topoisomerase inhibitors, NFkB/PI3/Akt/mTOR pathway inhibitors, through which these derivatives have shown promising anti-cancer potential. Results: A full literature review showed that the indole derivatives are associated with the properties of inducing apoptosis, aromatase inhibition, regulation of estrogen receptor and inhibition of tyrosine kinase, tubulin assembly, NFkB/PI3/Akt/mTOR pathway, and HDACs. These derivatives have shown significant activity against cancer cell lines. Conclusion: Indole derivatives seem to be important in cancer via acting through various mechanisms. This review has shown that the indole derivatives can further be explored for the betterment of cancer treatment, and to discover the hidden potential of indole derivatives.

scholarly journals Review On the Effects Curcumin on Tumors of the Reproductive System

2021 ◽  
Vol 10 ◽  
pp. e2178
Author(s):  
Zahra Moradi ◽  
Yasaman Hekmatnia ◽  
Amin Dalili ◽  
Mostafa Sadeghi ◽  
Seyed Sina Neshat ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cancer Cell ◽  
Reproductive System ◽  
Multiple Drug Resistance ◽  
Curcuma Longa ◽  
Cell Types ◽  
Multiple Drug ◽  
Protective Effects ◽  
Cancer Hallmarks ◽  
Anti Cancer

Curcumin, a polyphenolic derivative of Curcuma longa rhizome, has numerous beneficial effects, including antibacterial, anti-inflammatory, antiviral, antioxidant, antifungal, anti-ischemic, anti-cancer, hypoglycemic, nephroprotective, antirheumatic, hepato-protective, and antimutagenic. Curcumin has indicated the capability to exert anti-cancer activity by multifunctional mechanisms, such as induction of apoptosis, inhibition of cancer cell proliferation, cell cycle regulation, chemotherapeutic intestinal absorption, and modification of several cancer cell types signaling pathways. Several studies have shown that curcumin may have protective effects against tumors of the reproductive system. Reproductive system cancers may cause many undesirable physical and, especially, mental disorders. Infertility and its mental consequences, sexual problems, chemotherapy and surgery-related adverse effects, substantial economic burden, and death are the most common complications regarding the cancers of the reproductive system. By modulating several reproductive cancer hallmarks such as signaling pathways, multiple drug resistance, cancer cell growth and proliferation, tumor angiogenesis, and transcription factors, curcumin could be used as a safe, non-toxic, cheap, and easily accessible drug for treating different types of reproductive cancers. [GMJ.2021;10:e2178]

A Review of Anti-Cancer and Related Properties of Lichen-Extracts and Metabolites

2021 ◽  
Vol 21 ◽  
Author(s):  
Ankita H. Tripathi ◽  
Nidhi Negi ◽  
Rekha Gahtori ◽  
Amrita Kumari ◽  
Penny Joshi ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Multiple Drug Resistance ◽  
Usnic Acid ◽  
Multiple Drug ◽  
Proliferative Potential ◽  
Mesenchymal Transition ◽  
Anti Cancer ◽  
Lichen Substances ◽  
Lichen Metabolites ◽  
Anti Inflammatory

Background: Lichens are a composite consortium of fungus and alga. The symbiotic organisms are naturally equipped with distinct characteristics as compared to constituting organisms separately. Lichens due to their peculiar anatomy and physiology, are the reservoir of more than 600 unique secondary metabolites, also known as ‘lichen substances’. Since ancient times, many ethnic groups from various parts of the world had knowledge about the applications of lichens as major provenance of food/fodder, medicine, dyes, spices, perfumes, etc. Lichen substances have shown impressive antioxidant, antimicrobial, antiviral, antitumor, and anti-inflammatory activities under experimental conditions. Usnic acid, a well-known metabolite, found in several species of lichens, possesses potent antioxidant and anti-inflammatory activities. It also has significant anti-proliferative potential as revealed through testing in different cancer cell lines. Atranorin, Lecanoric acid, Norstictic acid, Lobaric acid, Stictic acid, Ramalin, Gyrophoric acid, Salazinic acid, Protolichesterinic, and Fumarprotocetraric acid are some of the other purified lichen metabolites with potent anti-cancer activities. Objective: This study presents an overview of lichen derived extracts/compounds augmenting the anti-cancer (related) properties. Method: The review comprehends different studies (in vivo and in vitro) backing up the possibility of lichen extracts and metabolites towards their use as antioxidant, anti-proliferative, anti-inflammatory and EMT-inhibiting agents. Results: The review focuses on anti-cancer and related properties of lichen extracts and metabolites that include their anti-oxidative, anti-inflammatory, anti-proliferative and pro-apoptotic, cancer stemness reduction, activities and, the potential of inhibition of cancer-associated Epithelial-mesenchymal transition (EMT) that is responsible for multiple drug-resistance and metastasis of cancer cells in a large proportion of cases. Conclusion: Lichens can be the repertoire of a plethora of lichen metabolites with putative bioactive potential, which is needed to be explored in order to find out novel anti-cancer drugs.

scholarly journals Advances in Therapeutic Implications of Inorganic Drug Delivery Nano-Platforms for Cancer

2019 ◽  
Vol 20 (4) ◽  
pp. 965 ◽  
Author(s):  
Safia Naz ◽  
Muhammad Shamoon ◽  
Rui Wang ◽  
Li Zhang ◽  
Juan Zhou ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Multiple Drug Resistance ◽  
Mesoporous Silica Nanoparticles ◽  
Superparamagnetic Iron Oxide ◽  
Chemotherapeutic Agents ◽  
Cancer Drug ◽  
Multiple Drug ◽  
Preclinical Development ◽  
Therapeutic Implications ◽  
Anti Cancer

Numerous nanoparticles drug delivery systems for therapeutic implications in cancer treatment are in preclinical development as conventional chemotherapy has several drawbacks. A chemotherapeutic approach requires high doses of chemotherapeutic agents with low bioavailability, non-specific targeting, and above all, development of multiple drug resistance. In recent years, inorganic nano-drug delivery platforms (NDDPs; with a metal core) have emerged as potential chemotherapeutic systems in oncology. One of the major goals of developing inorganic NDDPs is to effectively address the targeted anti-cancer drug(s) delivery related problems by carrying the therapeutic agents to desired tumors sites. In this current review, we delve into summarizing the recent developments in targeted release of anti-cancer drugs loaded in inorganic NDDPs such as mesoporous silica nanoparticles, carbon nanotubes, layered double hydroxides, superparamagnetic iron oxide nanoparticles and calcium phosphate nanoparticles together with highlighting their therapeutic performance at tumor sites.

Surgical Site Infections - A Hospital Havoc: Retrospective Study of Surgical Site Infections in Tertiary Health Care Centre in North East India

2018 ◽  
Vol 3 (01) ◽  
Author(s):  
V Singh ◽  
A B Khyriem, W V Lyngdoh ◽  
C J Lyngdoh
Keyword(s):  
Surgical Site Infection ◽  
Multiple Drug Resistance ◽  
Surgical Site Infections ◽  
Multidrug Resistant ◽  
Multiple Drug ◽  
Site Infection ◽  
Retrospective Case ◽  
Acinetobacter Baumanii ◽  
Health Care Centre ◽  
North East

Objectives - Surgical site infections (SSI) has turn out to be a major problem even in hospital with most modern facilities and standard protocols of pre -operative preparation and antibiotic prophylaxis. Objective of this study is to know the prevalence of surgical site infection among the postoperative patients and to identify the relationship between SSI and etiological pathogens along with their antimicrobial susceptibility at North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), Shillong. Methods - A retrospective case study conducted at NEIGRIHMS, among patients admitted to the surgical departments during the period between January 1st and December 31st 2016. Swabs from the surgical sites were collected under sterile conditions and standard bacteriological tests were performed for identification and appropriate statistical methods were employed to look for association between SSI and etiological pathogens. Results - Out of the 1284 samples included in the study, 192 samples showed evidence of SSI yielding an infection rate of 14.9%. The most commonly isolated bacteria were: Escherichia coli, Acinetobacter baumanii and Staphylococcus aureus, of the gram negative isolates 6.2% were multidrug resistant of which 19% were carbapenem resistant. Conclusion - SSI with multiple drug resistance strains and polymicrobial etiology reflects therapeutic failure. The outcome of the SSI surveillance in our hospital revealed that in order to decrease the incidence of SSI we would have to: a) incorporate a proper antibiotic stewardship  b) conduct periodic surveillance to keep a check on SSI d) educate medical staffs regarding the prevention of surgical site infection.

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