scholarly journals Cryptolepine consolidates its anticancer potential by increasing the anti-cancer pathway genes and decreasing that of pro-cancer pathway genes

2021 ◽  
Author(s):  
Patrick Williams Narkwa ◽  
Seth Agyei Domfeh ◽  
Gordon Awandare ◽  
Mohamed Mutocheluh
Keyword(s):  
Quantitative Polymerase Chain Reaction ◽  
Treatment Options ◽  
Hypoxia Inducible Factor ◽  
Signalling Pathways ◽  
Pharmacological Activities ◽  
Middle Income ◽  
Transcript Levels ◽  
Cryptolepis Sanguinolenta ◽  
Anti Cancer ◽  
Negative Side Effects

Abstract Background: Cancers are one of the commonest causes of deaths globally. Reports indicate that greater than sixty percent of cancers in the world occur in low and middle-income countries with about seventy percent of all cancer deaths occurring in these regions. Conventional cancer treatments involve surgery, radiotherapy, chemotherapy, etc. However, the negative side effects such as high cost and toxicity associated with these treatment options have increased the demand for less toxic and less expensive anti-cancer drugs from natural sources. One of such natural products believed to have anti-cancer potential is cryptolepine (CRYP), an alkaloid extracted from the roots of Western and Central African plant Cryptolepis sanguinolenta. In addition to its anti-cancer potential, CRYP has been reported to possess a myriad of pharmacological activities. However, the mechanisms underlying the anti-cancer and pharmacological activities of CRYP have not been fully explored. Methods: We screened 45 immune and cancer signalling pathways for their regulation following treatment with CRYP using the dual-luciferase based Cignal Finder Multi-Pathway Reporter Arrays to pinpoint which pathways are regulated by CRYP. Additionally, the effects of CRYP on the transcript levels of interferon regulatory factor 1 (IRF-1), progesterone receptor (PR), hypoxia-inducible factor-1 alpha (HIF-1α) and signal transducer and activator of transcription 3 (STAT 3) were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). Results: We observed that of the 45 immune and cancer signalling pathways screened, nine were up-regulated while twenty-seven were down-regulated by CRYP. However, CRYP had no effect on nine of the pathways screened. We also observed that CRYP induced an increase in the transcript levels of IRF1 and PR but decreased that of HIF1-α and STAT3. Conclusion: The upregulation of human anti-cancer pathway genes including IRF-1 and PR and concomitant down-regulation of pro-cancer pathway genes including HIF1-α and STAT3 suggest additional mechanisms through which CRYP could exhibits its anti-cancer potential.

scholarly journals Cryptolepine consolidates its anticancer potential by increasing the anti-cancer pathway genes and decreasing that of pro-cancer pathway genes

2021 ◽  
Author(s):  
Patrick Williams Narkwa ◽  
Seth Agyei Domfeh ◽  
Gordon Awandare ◽  
Mohamed Mutocheluh
Keyword(s):  
Quantitative Polymerase Chain Reaction ◽  
Treatment Options ◽  
Hypoxia Inducible Factor ◽  
Signalling Pathways ◽  
Pharmacological Activities ◽  
Middle Income ◽  
Transcript Levels ◽  
Cryptolepis Sanguinolenta ◽  
Anti Cancer ◽  
Negative Side Effects

Abstract Background: Cancers are one of the commonest causes of deaths globally. Reports indicate that greater than sixty percent of cancers in the world occur in low and middle-income countries with about seventy percent of all cancer deaths occurring in these regions. Conventional cancer treatments involve surgery, radiotherapy, chemotherapy, etc. However, the negative side effects such as high cost and toxicity associated with these treatment options have increased the demand for less toxic and less expensive anti-cancer drugs from natural sources. One of such natural products believed to have anti-cancer potential is cryptolepine (CRYP), an alkaloid extracted from the roots of Western and Central African plant Cryptolepis sanguinolenta. In addition to its anti-cancer potential, CRYP has been reported to possess a myriad of pharmacological activities. However, the mechanisms underlying the anti-cancer and pharmacological activities of CRYP have not been fully explored. Methods: We screened 45 immune and cancer signalling pathways for their regulation following treatment with CRYP using the dual-luciferase based Cignal Finder Multi-Pathway Reporter Arrays to pinpoint which pathways are regulated by CRYP. Additionally, the effects of CRYP on the transcript levels of interferon regulatory factor 1 (IRF-1), progesterone receptor (PR), hypoxia-inducible factor-1 alpha (HIF-1α) and signal transducer and activator of transcription 3 (STAT 3) were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). Results: We observed that of the 45 immune and cancer signalling pathways screened, nine were up-regulated while twenty-seven were down-regulated by CRYP. However, CRYP had no effect on nine of the pathways screened. We also observed that CRYP induced an increase in the transcript levels of IRF1 and PR but decreased that of HIF1-α and STAT3. Conclusion: The upregulation of human anti-cancer pathway genes including IRF-1 and PR and concomitant down-regulation of pro-cancer pathway genes including HIF1-α and STAT3 suggest additional mechanisms through which CRYP could exhibits its anti-cancer potential.

scholarly journals Cryptolepine consolidates its anticancer property by increasing the anti-cancer pathway genes and decreasing that of pro-cancer pathway genes

2020 ◽  
Author(s):  
Patrick Williams Narkwa ◽  
Seth Agyei Domfeh ◽  
Gordon Awandare ◽  
Mohamed Mutocheluh
Keyword(s):  
Quantitative Polymerase Chain Reaction ◽  
Treatment Options ◽  
Hypoxia Inducible Factor ◽  
Signalling Pathways ◽  
Pharmacological Activities ◽  
Middle Income ◽  
Transcript Levels ◽  
Anticancer Properties ◽  
Anti Cancer ◽  
Negative Side Effects

Abstract Background: Cancers are one of the commonest causes of deaths globally . Reports indicate that greater than sixty percent of cancers in the world occur in low and middle-income countries with about seventy percent of all cancer deaths occurring in these regions. Conventional cancer treatments involve surgery, radiotherapy, chemotherapy, etc. However, the negative side effects such as high cost and toxicity associated with these treatment options have increased the demand for less toxic and less expensive anti-cancer drugs from natural sources. One of such natural products believed to have anti-cancer potential is cryptolepine, an alkaloid extracted from the roots of Western and Central African plant Cryptolepis sanguinolenta . In addition to its anti-cancer potential, cryptolepine has been reported to possess a myriad of pharmacological activities. However, the mechanisms underlying the anti-cancer and pharmacological activities of cryptolepine have not been fully explored. The current study sought to determine the mechanism underlying the anticancer properties of cryptolepine. Methods: We screened 45 immune and cancer signalling pathways for their regulation following treatment with cryptolepine using the dual-luciferase based Cignal Finder Multi-Pathway Reporter Arrays to pinpoint which pathways are regulated by cryptolepine. Additionally, the effects of cryptolepine on the transcript levels of interferon regulatory factor 1(IRF1), progesterone receptor (PR), hypoxia-inducible factor-1 alpha (HIF-1α) and signal transducer and activator of transcription 3 (STAT3) were assessed by real-time quantitative polymerase chain reaction. Results: We observed that of the 45 immune and cancer signalling pathways screened, nine were up-regulated while twenty-seven were down-regulated by cryptolepine. However, cryptolepine had no effect on nine of the pathways screened. We also observed that cryptolepine induced an increase in the transcript levels of IRF1 and PR but decreased that of HIF1-α and STAT3. Conclusion: The upregulation of human anti-cancer pathway genes including IRF-1 and PR and concomitant down-regulation of pro-cancer pathway genes including HIF1-α and STAT3 suggest additional mechanisms through which cryptolepine exhibits its anti-cancer activities.

scholarly journals Cryptolepine inhibits hepatocellular carcinoma growth through inhibiting interleukin-6/STAT3 signalling

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Seth A. Domfeh ◽  
Patrick W. Narkwa ◽  
Osbourne Quaye ◽  
Kwadwo A. Kusi ◽  
Gordon A. Awandare ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Interleukin 6 ◽  
Signalling Pathway ◽  
Signalling Pathways ◽  
Human Hepatoma Cells ◽  
Cryptolepis Sanguinolenta ◽  
Anti Cancer ◽  
Dose Dependent Fashion ◽  
Cancer Intervention ◽  
Stat3 Signalling

Abstract Background Diverse signalling pathways are involved in carcinogenesis and one of such pathways implicated in many cancers is the interleukin 6/signal transducer and activator of transcription 3 (IL-6/STAT3) signalling pathway. Therefore, inhibition of this pathway is targeted as an anti-cancer intervention. This study aimed to establish the effect of cryptolepine, which is the main bioactive alkaloid in the medicinal plant Cryptolepis sanguinolenta, on the IL-6/STAT3 signalling pathway. Methods First, the effect of cryptolepine on the IL-6/STAT3 pathway in human hepatoma cells (HepG2 cells) was screened using the Cignal Finder Multi-Pathway Reporter Array. Next, to confirm the effect of cryptolepine on the IL-6/STAT3 signalling pathway, the pathway was activated using 200 ng/mL IL-6 in the presence of 0.5–2 μM cryptolepine. The levels of total STAT3, p-STAT3 and IL-23 were assessed by ELISA. Results Cryptolepine downregulated 12 signalling pathways including the IL-6/STAT3 signalling pathway and upregulated 17 signalling pathways. Cryptolepine, in the presence of IL-6, decreased the levels of p-STAT3 and IL-23 in a dose-dependent fashion. Conclusion Our results demonstrated that cryptolepine inhibits the IL-6/STAT3 signalling pathway, and therefore cryptolepine-based remedies such as Cryptolepis sanguinolenta could potentially be used as an effective immunotherapeutic agent for hepatocellular carcinoma and other cancers.

Anticancer Activity of Natural Flavonoids: Inhibition of HIF-1α Signaling Pathway

2020 ◽  
Vol 23 (26) ◽  
pp. 2945-2959 ◽  
Author(s):  
Xiangping Deng ◽  
Yijiao Peng ◽  
Jingduo Zhao ◽  
Xiaoyong Lei ◽  
Xing Zheng ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Secondary Metabolites ◽  
Anticancer Agents ◽  
Hypoxia Inducible Factor ◽  
Tumor Hypoxia ◽  
Pharmacological Activities ◽  
Hypoxia Inducible Factor 1 ◽  
The Past ◽  
Low Toxicity ◽  
Tumor Blood Vessels

Rapid tumor growth is dependent on the capability of tumor blood vessels and glycolysis to provide oxygen and nutrients. Tumor hypoxia is a common characteristic of many solid tumors, and it essentially happens when the growth of the tumor exceeds the concomitant angiogenesis. Hypoxia-inducible factor 1 (HIF-1) as the critical transcription factor in hypoxia regulation is activated to adapt to this hypoxia situation. Flavonoids, widely distributed in plants, comprise many polyphenolic secondary metabolites, possessing broadspectrum pharmacological activities, including their potentiality as anticancer agents. Due to their low toxicity, intense efforts have been made for investigating natural flavonoids and their derivatives that can be used as HIF-1α inhibitors for cancer therapy during the past few decades. In this review, we sum up the findings concerning the inhibition of HIF-1α by natural flavonoids in the last few years and propose the idea of designing tumor vascular and glycolytic multi-target inhibitors with HIF-1α as one of the targets.

Ethnomedicinal uses, Phytochemistry and Pharmacological Aspects of the Genus Berberis Linn: A Comprehensive Review

2020 ◽  
Vol 23 ◽  
Author(s):  
Roohi Mohi-ud-din ◽  
Reyaz Hassan Mir ◽  
Prince Ahad Mir ◽  
Saeema Farooq ◽  
Syed Naiem Raza ◽  
...  
Keyword(s):  
Chemical Constituents ◽  
Pharmacological Activities ◽  
Traditional Use ◽  
Comprehensive Review ◽  
Wide Range ◽  
Anti Cancer ◽  
Comprehensive Survey ◽  
Ethnomedicinal Uses

Background: Genus Berberis (family Berberidaceae), which contains about 650 species and 17 genera worldwide, has been used in folklore and various traditional medicine systems. Berberis Linn. is the most established group among genera with around 450-500 species across the world. This comprehensive review will not only help researchers for further evaluation but also provide substantial information for future exploitation of species to develop novel herbal formulations. Objective: The present review is focussed to summarize and collect the updated review of information of Genus Berberis species reported to date regarding their ethnomedicinal information, chemical constituents, traditional/folklore use, and reported pharmacological activities on more than 40 species of Berberis. Conclusion: A comprehensive survey of the literature reveals that various species of the genus possess various phytoconstituents mainly alkaloids, flavonoid based compounds isolated from different parts of a plant with a wide range of pharmacological activities. So far, many pharmacological activities like anti-cancer, anti-hyperlipidemic, hepatoprotective, immunomodulatory, anti-inflammatory both in vitro & in vivo and clinical study of different extracts/isolated compounds of different species of Berberis have been reported, proving their importance as a medicinal plant and claiming their traditional use.

Phytochemical, Pharmacological Activities and Ayurvedic Significances of Magical Plant Mimosa pudica Linn

2020 ◽  
Vol 17 ◽  
Author(s):  
Vijay Kumar
Keyword(s):  
Therapeutic Potential ◽  
Wide Spectrum ◽  
Chemical Constituents ◽  
Future Research ◽  
Mimosa Pudica ◽  
Pharmacological Activities ◽  
Medicinal Uses ◽  
Traditional Medicines ◽  
Crude Extracts ◽  
Anti Cancer

: Mimosa pudica Linn is an integrated part of Traditional Medicines Systems of India, China, Africa, Korea and America. It has been used from centuries in traditional medicines to cure different diseases like fever, diabetes, constipation, jaundice, ulcers, biliousness, and dyspepsia. It is an important ingredient of wide class of herbal formulations. To assess the scientific evidence for therapeutic potential of Mimosa pudica Linn and to identify the gaps for future research. The available information on the ethno-medicinal uses, phytochemistry, pharmacology and toxicology of Mimosa pudica Linn was collected via a library and electronic searches in Sci-Finder, Pub-Med, Science Direct, Google Scholar for the period, 1990 to 2020. In traditional medicinal systems, variety of ethno-medicinal applications of Mimosa pudica Linn has been noticed. Phytochemical investigation has resulted in identification of 40 well known chemical constituents, among which alkaloids, phenols and flavionoids are the predominant groups. The crude extracts and isolates have exhibited a wide spectrum of in vitro and in vivo pharmacological activities including anti-cancer, anti-inflammation, osteoporosis, neurological disorders, hypertension etc.. To quantify the Mimosa pudica Linn and its formulations, analytical techniques like HPLC and HPTLC has shown dominancy with good range of recovery and detection limit. Mimosa pudica Linn is the well-known herb since an ancient time. The pharmacological results supported some of the applications of Mimosa pudica Linn in traditional medicine systems. Perhaps, the predominance of alkaloids, phenols and flavionoids are responsible for the pharmacological activities the crude extracts and isolates of Mimosa pudica Linn. Further, there is need to isolate and evaluate the active chemical constituents of Mimosa pudica Linn having significant medicinal values. In future, it is important to study the exact mechanism associated with the phytochemicals of Mimosa pudica Linn especially on anti-cancer activities. Notably, toxicity studies on Mimosa pudica Linn are limited which are to be explored in future for the safe application of Mimosa pudica Linn and its formulations.

scholarly journals Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Marjan Talebi ◽  
Mohsen Talebi ◽  
Tahereh Farkhondeh ◽  
Jesus Simal-Gandara ◽  
Dalia M. Kopustinskiene ◽  
...  
Keyword(s):  
Blood Cells ◽  
Molecular Mechanisms ◽  
Web Of Science ◽  
Experimental Studies ◽  
Protective Effects ◽  
Pharmacological Activities ◽  
Current Review ◽  
Mesh Terms ◽  
Online Databases ◽  
Anti Cancer

AbstractChrysin has been shown to exert several beneficial pharmacological activities. Chrysin has anti-cancer, anti-viral, anti-diabetic, neuroprotective, cardioprotective, hepatoprotective, and renoprotective as well as gastrointestinal, respiratory, reproductive, ocular, and skin protective effects through modulating signaling pathway involved in apoptosis, oxidative stress, and inflammation. In the current review, we discussed the emerging cellular and molecular mechanisms underlying therapeutic indications of chrysin in various cancers. Online databases comprising Scopus, PubMed, Embase, ProQuest, Science Direct, Web of Science, and the search engine Google Scholar were searched for available and eligible research articles. The search was conducted by using MeSH terms and keywords in title, abstract, and keywords. In conclusion, experimental studies indicated that chrysin could ameliorate cancers of the breast, gastrointestinal tract, liver and hepatocytes, bladder, male and female reproductive systems, choroid, respiratory tract, thyroid, skin, eye, brain, blood cells, leukemia, osteoblast, and lymph. However, more studies are needed to enhance the bioavailability of chrysin and evaluate this agent in clinical trial studies. Graphic abstract

Gonadotrophins modulate cell death-related genes expression in human endometrium

2020 ◽  
Vol 41 (2) ◽  
Author(s):  
Sandro Sacchi ◽  
Paola Sena ◽  
Chiara Addabbo ◽  
Erika Cuttone ◽  
Antonio La Marca
Keyword(s):  
Cell Death ◽  
Quantitative Polymerase Chain Reaction ◽  
Hypoxia Inducible Factor ◽  
Endometrial Cells ◽  
Microtubule Associated Proteins ◽  
Genes Expression ◽  
Associated Proteins ◽  
Polymerase Chain ◽  
Cytochrome P450 Family ◽  
Apoptosis Marker

AbstractBackgroundGonadotrophins exert their functions by binding follicle-stimulating hormone receptor (FSHR) or luteinizing hormone and human chorionic gonadotropin receptor (LHCGR) present on endometrium. Within ovaries, FSH induces autophagy and apoptosis of granulosa cells leading to atresia of non-growing follicles, whereas hCG and LH have anti-apoptotic functions. Endometrial cells express functioning gonadotrophin receptors. The objective of this study was to analyze the effect of gonadotrophins on physiology and endometrial cells survival.Materials and methodsCollected endometria were incubated for 48 or 72 h with 100 ng/mL of recombinant human FSH (rhFSH), recombinant human LH (rhLH) or highly purified hCG (HPhCG) alone or combined. Controls omitted gonadotrophins. The effect of gonadotrophins on cytochrome P450 family 11 subfamily A polypeptide 1 (CYP11A1), hypoxia inducible factor 1α (HIF1A), and cell-death-related genes expression was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Immunohistochemistry for microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) and apoptotic protease activating factor 1 (APAF-1) was performed.ResultsGonadotrophins are able to modulate the endometrial cells survival. FSH induced autophagy and apoptosis by increasing the relative expression of MAP1LC3B and FAS receptor. In FSH-treated samples, expression of apoptosis marker APAF-1 was detected and co-localized on autophagic cells. hCG and LH does not modulate the expression of cell-death-related genes while the up-regulation of pro-proliferative epiregulin gene was observed. When combined with FSH, hCG and LH prevent autophagy and apoptosis FSH-induced.ConclusionsDifferent gonadotrophins specifically affect endometrial cells viability differently: FSH promotes autophagy and apoptosis while LH and hCG alone or combined with rhFSH does not.

scholarly journals Hypoxia-inducible Factor 2α: A Key Player in Tumorigenesis and Metastasis of Pheochromocytoma and Paraganglioma?

2021 ◽  
Author(s):  
Nicole Bechmann ◽  
Graeme Eisenhofer
Keyword(s):  
Extracellular Matrix ◽  
Signaling Pathways ◽  
Metastatic Disease ◽  
Therapeutic Intervention ◽  
Treatment Options ◽  
Hypoxia Inducible Factor ◽  
Germline Mutations ◽  
Driver Mutations ◽  
Mesenchymal Transition ◽  
Therapeutic Relevance

AbstractGermline or somatic driver mutations linked to specific phenotypic features are identified in approximately 70% of all catecholamine-producing pheochromocytomas and paragangliomas (PPGLs). Mutations leading to stabilization of hypoxia-inducible factor 2α (HIF2α) and downstream pseudohypoxic signaling are associated with a higher risk of metastatic disease. Patients with metastatic PPGLs have a variable prognosis and treatment options are limited. In most patients with PPGLs, germline mutations lead to the stabilization of HIF2α. Mutations in HIF2α itself are associated with adrenal pheochromocytomas and/or extra-adrenal paragangliomas and about 30% of these patients develop metastatic disease; nevertheless, the frequency of these specific mutations is low (1.6–6.2%). Generally, mutations that lead to stabilization of HIF2α result in distinct catecholamine phenotype through blockade of glucocorticoid-mediated induction of phenylethanolamine N-methyltransferase, leading to the formation of tumors that lack epinephrine. HIF2α, among other factors, also contributes importantly to the initiation of a motile and invasive phenotype. Specifically, the expression of HIF2α supports a neuroendocrine-to-mesenchymal transition and the associated invasion-metastasis cascade, which includes the formation of pseudopodia to facilitate penetration into adjacent vasculature. The HIF2α-mediated expression of adhesion and extracellular matrix genes also promotes the establishment of PPGL cells in distant tissues. The involvement of HIF2α in tumorigenesis and in multiple steps of invasion-metastasis cascade underscores the therapeutic relevance of targeting HIF2α signaling pathways in PPGLs. However, due to emerging resistance to current HIF2α inhibitors that target HIF2α binding to specific partners, alternative HIF2α signaling pathways and downstream actions should also be considered for therapeutic intervention.

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