scholarly journals Molecular and Cellular Mechanisms of Metformin in Cervical Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2545
Author(s):  
Ya-Hui Chen ◽  
Po-Hui Wang ◽  
Pei-Ni Chen ◽  
Shun-Fa Yang ◽  
Yi-Hsuan Hsiao
Keyword(s):  
Cervical Cancer ◽  
Potential Role ◽  
Treatment Options ◽  
Cellular Mechanisms ◽  
Anticancer Effects ◽  
Clinical Benefits ◽  
Underlying Mechanisms

Cervical cancer is one of the major gynecologic malignancies worldwide. Treatment options include chemotherapy, surgical resection, radiotherapy, or a combination of these treatments; however, relapse and recurrence may occur, and the outcome may not be favorable. Metformin is an established, safe, well-tolerated drug used in the treatment of type 2 diabetes; it can be safely combined with other antidiabetic agents. Diabetes, possibly associated with an increased site-specific cancer risk, may relate to the progression or initiation of specific types of cancer. The potential effects of metformin in terms of cancer prevention and therapy have been widely studied, and a number of studies have indicated its potential role in cancer treatment. The most frequently proposed mechanism underlying the diabetes–cancer association is insulin resistance, which leads to secondary hyperinsulinemia; furthermore, insulin may exert mitogenic effects through the insulin-like growth factor 1 (IGF-1) receptor, and hyperglycemia may worsen carcinogenesis through the induction of oxidative stress. Evidence has suggested clinical benefits of metformin in the treatment of gynecologic cancers. Combining current anticancer drugs with metformin may increase their efficacy and diminish adverse drug reactions. Accumulating evidence is indicating that metformin exerts anticancer effects alone or in combination with other agents in cervical cancer in vitro and in vivo. Metformin might thus serve as an adjunct therapeutic agent for cervical cancer. Here, we reviewed the potential anticancer effects of metformin against cervical cancer and discussed possible underlying mechanisms.

Phytosomal Curcumin Elicits Anti-tumor Properties Through Suppression of Angiogenesis, Cell Proliferation and Induction of Oxidative Stress in Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4626-4638 ◽  
Author(s):  
Reyhaneh Moradi-Marjaneh ◽  
Seyed M. Hassanian ◽  
Farzad Rahmani ◽  
Seyed H. Aghaee-Bakhtiari ◽  
Amir Avan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Therapeutic Potential ◽  
Vegf Signaling ◽  
Anticancer Effects ◽  
Inhibition Of Angiogenesis ◽  
Underlying Mechanisms ◽  
Apoptotic Activity

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality in the world. Anti-tumor effect of curcumin has been shown in different cancers; however, the therapeutic potential of novel phytosomal curcumin, as well as the underlying molecular mechanism in CRC, has not yet been explored. Methods: The anti-proliferative, anti-migratory and apoptotic activity of phytosomal curcumin in CT26 cells was assessed by MTT assay, wound healing assay and Flow cytometry, respectively. Phytosomal curcumin was also tested for its in-vivo activity in a xenograft mouse model of CRC. In addition, oxidant/antioxidant activity was examined by DCFH-DA assay in vitro, measurement of malondialdehyde (MDA), Thiol and superoxidedismutase (SOD) and catalase (CAT) activity and also evaluation of expression levels of Nrf2 and GCLM by qRT-PCR in tumor tissues. In addition, the effect of phytosomal curcumin on angiogenesis was assessed by the measurement of VEGF-A and VEGFR-1 and VEGF signaling regulatory microRNAs (miRNAs) in tumor tissue. Results: Phytosomal curcumin exerts anti-proliferative, anti-migratory and apoptotic activity in-vitro. It also decreases tumor growth and augmented 5-fluorouracil (5-FU) anti-tumor effect in-vivo. In addition, our data showed that induction of oxidative stress and inhibition of angiogenesis through modulation of VEGF signaling regulatory miRNAs might be underlying mechanisms by which phytosomal curcumin exerted its antitumor effect. Conclusion: Our data confirmed this notion that phytosomal curcumin administrates anticancer effects and can be used as a complementary treatment in clinical settings.

scholarly journals The Anticancer Effects of Paeoniflorin and Its Underlying Mechanisms

2019 ◽  
Vol 14 (9) ◽  
pp. 1934578X1987640
Author(s):  
Li-Juan Deng ◽  
Yu-He Lei ◽  
Tsz-Fung Chiu ◽  
Ming Qi ◽  
Hua Gan ◽  
...  
Keyword(s):  
Recent Progress ◽  
Antitumor Effect ◽  
Molecular Mechanisms ◽  
Experimental Studies ◽  
Future Prospects ◽  
Anticancer Effects ◽  
Wide Range ◽  
Underlying Mechanisms

Paeoniflorin (PF) is an important pharmacological component of some Chinese traditional herbal formulas, such as Bai Shao, Chi Shao, and Dan Pi, which have been clinically used for centuries. Although many experimental studies have explored a wide range of pharmacological properties of PF, including anticancer, anti-inflammatory, antioxidant, immunoregulatory, and prevention of insulin resistance, there is no review to describe these reported effects systematically, especially the antitumor effect and the underlying mechanisms. In this review, we summarize the recent progress on the anticancer profiles both in vitro and in vivo of PF. Moreover, we highlight the integrated molecular mechanisms of PF and contemplate its future prospects as a potential anticancer drug.

scholarly journals Ganoderma lucidum Polysaccharides as An Anti-cancer Agent

2018 ◽  
Vol 18 (5) ◽  
pp. 667-674 ◽  
Author(s):  
Didem Sohretoglu ◽  
Shile Huang
Keyword(s):  
Ganoderma Lucidum ◽  
Water Soluble ◽  
In Vivo Studies ◽  
Beneficial Effects ◽  
Anticancer Effects ◽  
Bioactive Component ◽  
Cancer Agent ◽  
Underlying Mechanisms

The mushroom Ganoderma lucidum (G. lucidum) has been used for centuries in Asian countries to treat various diseases and to promote health and longevity. Clinical studies have shown beneficial effects of G. lucidum as an alternative adjuvant therapy in cancer patients without obvious toxicity. G. lucidum polysaccharides (GLP) is the main bioactive component in the water soluble extracts of this mushroom. Evidence from in vitro and in vivo studies has demonstrated that GLP possesses potential anticancer activity through immunomodulatory, anti-proliferative, pro-apoptotic, anti-metastatic and anti-angiogenic effects. Here, we briefly summarize these anticancer effects of GLP and the underlying mechanisms.

scholarly journals PPAR-γAgonists and Their Effects on IGF-I Receptor Signaling: Implications for Cancer

PPAR Research ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-18 ◽  
Author(s):  
A. Belfiore ◽  
M. Genua ◽  
R. Malaguarnera
Keyword(s):  
Therapeutic Approaches ◽  
Cancer Risk Factor ◽  
Multiple Components ◽  
Igf System ◽  
Anticancer Effects ◽  
Insulin Sensitizers ◽  
Igf I

It is now well established that the development and progression of a variety of human malignancies are associated with dysregulated activity of the insulin-like growth factor (IGF) system. In this regard, promising drugs have been developed to target the IGF-I receptor or its ligands. These therapies are limited by the development of insulin resistance and compensatory hyperinsulinemia, which in turn, may stimulate cancer growth. Novel therapeutic approaches are, therefore, required. Synthetic PPAR-γagonists, such as thiazolidinediones (TZDs), are drugs universally used as antidiabetic agents in patients with type 2 diabetes. In addition of acting as insulin sensitizers, PPAR-γagonists mediate in vitro and in vivo pleiotropic anticancer effects. At least some of these effects appear to be linked with the downregulation of the IGF system, which is induced by the cross-talk of PPAR-γagonists with multiple components of the IGF system signaling. As hyperinsulinemia is an emerging cancer risk factor, the insulin lowering action of PPAR-γagonists may be expected to be also beneficial to reduce cancer development and/or progression. In light of these evidences, TZDs or other PPAR-γagonists may be exploited in those tumors “addicted” to the IGF signaling and/or in tumors occurring in hyperinsulinemic patients.

scholarly journals Downregulation of NCL attenuates tumor formation and growth in cervical cancer by targeting the PI3K/AKT pathway

2021 ◽  
Author(s):  
Jun Ying ◽  
Ruowang Pan ◽  
Zhouhao Tang ◽  
Jiayin Zhu ◽  
Ping Ren ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Opposite Effect ◽  
Vital Role ◽  
Tumor Formation ◽  
Akt Pathway ◽  
Pi3k Inhibitor Ly294002 ◽  
Proliferation And Apoptosis ◽  
Underlying Mechanisms

AbstractNucleolin (NCL, C23) is a multifunctional phosphoprotein that plays a vital role in modulating the survival, proliferation and apoptosis of cancer cells. However, the effects of NCL on cervical cancer and the underlying mechanisms behind this are poorly understood. In the study presented here, Hela cells were transfected with shRNAs targeting the endogenous NCL gene (sh-NCL-Hela). NCL knockdown inhibited cell proliferation and promoted apoptosis both in vivo and in vitro. Mechanistic studies revealed that NCL knockdown inhibited the PI3K/AKT pathway by upregulating FGF, ITGA, TNXB, VEGF, Caspase 3, and Bax, as well as by downregulating AKT, GNB4, CDK6, IL6R, LAMA, PDGFD, PPP2RSA and BCL-2. In addition, the expression levels of apoptosis-related genes after using a PI3K inhibitor LY294002 were consistent with shRNA studies, while treatment with a 740Y-P agonist showed the opposite effect. Altogether, this study uncovered that downregulation of NCL may be a novel treatment strategy for cervical cancer.

scholarly journals CDK12 Promotes Cervical Cancer Progression through Enhancing Macrophage Infiltration

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Bikang Yang ◽  
Jing Chen ◽  
Yincheng Teng
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Therapeutic Target ◽  
Macrophage Infiltration ◽  
Patient Death ◽  
Mrna And Protein Expression ◽  
Underlying Mechanisms

Cervical cancer (CC) is a commonly diagnosed and primary consideration of cancer patient death in female reproductive system malignancy. Cyclin-dependent kinase 12 (CDK12), as a transcription-associated CDK, plays important roles in tumor-promoting behaviors, whereas the underlying mechanisms of CDK12 in CC progression are still obscure. In this report, we investigated the role of CDK12 in cervical cancer. The current study identified CDK12 mRNA and protein expression remarkably upregulated in CC patients. Upregulated CDK12 was closely associated with CC progression and poor prognosis. In vitro and in vivo functional experiments showed that knockdown of CDK12 inhibited cancer cell proliferation and colony formation and promoted apoptosis. Further investigations demonstrated that CDK12 regulated the immune microenvironment to facilitate the progression of CC cells by promoting macrophage infiltration. Meanwhile, we first demonstrated that nuclear import of CDK12 is mediated by TNPO1 and might be a new therapeutic target in oncology. Collectively, this study pointed out the potential of CDK12 to serve as a novel therapeutic target in restricting CC proliferation and cell cycle process through promoting macrophage infiltration.

scholarly journals Therapeutic Value of 6-Gingerol (1-[4′-hydroxy-3′-methoxyphenyl]-5-hydroxy-3-decanone): A Review

2021 ◽  
pp. 63-75
Author(s):  
Girum Tefera Belachew ◽  
Bitaniya Abera Tekelemariam ◽  
Paramesh Hanumanthaiah ◽  
Fekede Meshesha Namo
Keyword(s):  
Fruits And Vegetables ◽  
Zingiber Officinale ◽  
Cytotoxic Action ◽  
Anticancer Effects ◽  
Therapeutic Value ◽  
Anti Cancer ◽  
Underlying Mechanisms ◽  
And Control

Utilization of crude extracts separated from herbal medicine is getting more worthy and ideal, conceivably because of the expense of production, accessibility and availability to bring down harmful effects as much as possible. Various researches have shown that the regular use of particular soil products like fruits and vegetables can minimize the risk of a number of infections. Ginger is among the most commonly and regularly devoured dietary sauces on the planet. One of the major impactful components of ginger, 6-gingerol is suggested for the avoidance of malignancy and different maladies. As a spice and home grown medicine, the rhizome of Zingiber officinale (ginger) is devoured worldwide and it contains sharp phenolic compounds known as gingerols aggregately. The main pharmacologically-dynamic segment of ginger is 6-Gingerol. It is recognized to show a variety of organic actions including anti-cancer, anti-inflammation, and anti-oxidation. 6-Gingerol has been found to have anticancer effects by means of its impact on an assortment of natural pathways associated with apoptosis, control of cell cycle, cytotoxic action and restraint of angiogenesis. Consequently, because of its adequacy and control of different targets, just as its security for human use, 6-gingerol has gained impressive enthusiasm as an expected helpful operator for the anticipation and additionally treatment for different maladies. Taken together, this review sums up the different in vitro and in vivo pharmacological aspects of 6-gingerol and their underlying mechanisms.

scholarly journals The Potential of Chinese Herbal Medicines in the Treatment of Cervical Cancer

2019 ◽  
Vol 18 ◽  
pp. 153473541986169 ◽  
Author(s):  
Yi-Hsuan Hsiao ◽  
Chiao-Wen Lin ◽  
Po-Hui Wang ◽  
Min-Chien Hsin ◽  
Shun-Fa Yang
Keyword(s):  
Cervical Cancer ◽  
Treatment Options ◽  
Herbal Medicines ◽  
Antitumor Effects ◽  
Clinical Safety ◽  
Chinese Herbal Medicines ◽  
Chinese Herbal ◽  
Global Health Issue ◽  
Underlying Mechanisms

Cervical cancer is a global health issue and places a considerable economic and medical burden on society. Thus, a concerted effort to improve the treatment of cervical cancer is warranted. Although several treatment options are currently available for treating patients with cervical cancer, such as chemoradiation and neoadjuvant or adjuvant chemotherapy, more aggressive systemic therapies and newer therapeutic agents are under investigation. Medicinal herbs have long been used to treat diseases. In this review, we summarize studies analyzing the antitumor effects and underlying mechanisms of Chinese herbal medicines, including the effects of crude extracts and compounds in vitro or in animal models for inducing apoptosis and inhibiting invasion or metastasis. Chinese herbal medicines with therapeutic targeting, such as those that interfere with tumor growth and progression in cervical cancer, have been widely investigated. To apply Chinese herbal medicine in the treatment of cervical cancer, adequate clinical studies are required to confirm its clinical safety and efficiency. Further investigations focused on the purification, pharmacokinetics, and identification of compounds from Chinese herbal medicines in cervical cancer treatment are necessary to achieve the aforementioned treatment goals.

scholarly journals PDCD4 deficiency ameliorates left ventricular remodeling and insulin resistance in a rat model of type 2 diabetic cardiomyopathy

2020 ◽  
Vol 8 (1) ◽  
pp. e001081
Author(s):  
Jie Zhang ◽  
Meng Zhang ◽  
Zhi Yang ◽  
Shanying Huang ◽  
Xiao Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cardiac Remodeling ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Akt Pathway ◽  
Underlying Mechanisms

ObjectiveDiabetic cardiomyopathy (DCM) is characterized by cardiac remodeling, dysfunction, and insulin resistance; however, the underlying mechanism has not been fully elucidated. Programmed cell death 4 (PDCD4) is a novel inflammation and apoptosis gene, but its role in type 2 DCM remains elusive. We aimed to determine if PDCD4 intervention improves DCM by affecting left ventricular remodeling, function, and insulin resistance.Research design and methodsWe designed a PDCD4-/- rat, established a type 2 diabetes animal model, and constructed a PDCD4 overexpressed adenovirus and PDCD4 small interfer RNA (siRNA) vectors to alter PDCD4 expression in H9c2 cardiomyocytes. Thereafter, glucose levels, lipid metabolism, echocardiography, and extent of myocardial fibrosis, inflammation, and apoptosis were compared in vivo and in vitro.ResultsPDCD4 deficiency improved insulin resistance, cardiac remodeling, and dysfunction in type 2 DCM rats and improved myocardial hypertrophy, fibrosis, inflammation, and apoptosis. Proliferation and transformation of cardiac fibroblasts was reduced via PDCD4 downregulation in vitro under high-glucose stimulation. Furthermore, PDCD4 regulated the myocardial phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) pathway in vivo and in vitro. PDCD4 intervention affected cardiac remodeling, dysfunction, and insulin resistance by influencing fibrosis, inflammation, and apoptosis via the PI3K-AKT pathway in vivo.ConclusionsPDCD4 knockdown protected against left ventricular remodeling, dysfunction, and insulin resistance in type 2 DCM rats. The underlying mechanisms may involve reducing cardiomyocyte apoptosis, inflammation, fibrosis, and normalized PI3K-AKT phosphorylation. To the best of our knowledge, our study is the first to report the effects and underlying mechanisms of PDCD4 in type 2 DCM. These results provide a potential new treatment avenue for improving the prognosis of patients with type 2 DCM.

scholarly journals Diabetes confers in vitro calcific potential on serum which associates with in vivo vascular calcification

2017 ◽  
Vol 131 (10) ◽  
pp. 991-1000 ◽  
Author(s):  
Ashish Patidar ◽  
Dhruv K. Singh ◽  
Shori Thakur ◽  
Peter Winocour ◽  
Ken Farrington ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Vascular Calcification ◽  
Matrix Gla Protein ◽  
Aortic Smooth Muscle ◽  
C Statistic ◽  
Underlying Mechanisms ◽  
Operator Curve

Although vascular calcification (VC) is prevalent in Type 2 diabetes mellitus (T2DM), underlying mechanisms remain unclear. Neither is it known whether T2DM confers calcific potential (CP) on serum, enabling it to induce VC outside the disease milieu. We, therefore, investigated the CP of serum from controls and subjects with T2DM with and without in vivo VC. Samples from 20 healthy controls and 44 age- and sex-matched patients with T2DM with modification of diet in renal disease estimated glomerular filtration rate (MDRD-4 eGFR) > 60 ml·min−1 were analysed for CP using rat aortic smooth muscle cells in vitro. CT scans of femoral arteries identified individuals with in vivo calcification. Serum from subjects with T2DM revealed significantly greater CP than controls. This was further enhanced in the presence of in vivo VC. Addition of β-glycerophosphate (β-GP) plus CaCl2 increased the CP of T2DM serum but not of controls. Along with age, CP was an independent predictor of the presence of VC. In receiver operator curve (ROC) analysis, CP was a significant predictor of femoral arterial VC (C-statistic 0.70: P=0.009). The distribution of CP was bimodal around a cutoff of 100 nmoles of Ca2+ protein mg−1, with a higher proportion of Type 2 diabetes subjects with in vivo calcification (T2DM+) sera above the cutoff value. This group also showed elevated levels of osteoprotegerin (OPG) and matrix Gla protein (MGP). Diabetes confers CP on the serum which is enhanced by the presence of in vivo VC. The CP acquired may be dependent on levels of OPG and MGP. These findings may be clinically relevant for early identification of individuals at risk of VC and for informing therapeutic strategies.

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