scholarly journals Punicalagin in Cancer Prevention—Via Signaling Pathways Targeting

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2733
Author(s):  
Izabela Berdowska ◽  
Małgorzata Matusiewicz ◽  
Izabela Fecka

The extract of pomegranate (Punica granatum) has been applied in medicine since ancient times due to its broad-spectrum health-beneficial properties. It is a rich source of hydrolyzable tannins and anthocyanins, exhibiting strong antioxidative, anti-inflammatory, and antineoplastic properties. Anticancer activities of pomegranate with reference to modulated signaling pathways in various cancer diseases have been recently reviewed. However, less is known about punicalagin (Pug), a prevailing compound in pomegranate, seemingly responsible for its most beneficial properties. In this review, the newest data derived from recent scientific reports addressing Pug impact on neoplastic cells are summarized and discussed. Its attenuating effect on signaling circuits promoting cancer growth and invasion is depicted. The Pug-induced redirection of signal-transduction pathways from survival and proliferation into cell-cycle arrest, apoptosis, senescence, and autophagy (thus compromising neoplastic progression) is delineated. Considerations presented in this review are based mainly on data obtained from in vitro cell line models and concern the influence of Pug on human cervical, ovarian, breast, lung, thyroid, colorectal, central nervous system, bone, as well as other cancer types.

Oncotarget ◽  
2016 ◽  
Vol 7 (16) ◽  
pp. 22409-22426 ◽  
Author(s):  
You-Cheng Hseu ◽  
Varadharajan Thiyagarajan ◽  
Hsiao-Tung Tsou ◽  
Kai-Yuan Lin ◽  
Hui-Jye Chen ◽  
...  

2019 ◽  
Vol 6 (4) ◽  
pp. 58-68
Author(s):  
T. I. Fetisov ◽  
K. I. Kirsanov ◽  
A. A. Borunova ◽  
M. N. Zatsepina ◽  
E. A. Lesovaya ◽  
...  

Background. Curaxin CBL0137 is a novel non-genotoxic compound with anti-cancer activity based on CBL0137 ability of non-covalent interaction with DNA causing histone chaperone FACT relocation. Anti-cancer activity of this drug was demonstrated previously on the wide panel of solid cancer models in vitro and in vivo.Objectives. Estimation of anticancer effects of CBL0137 on the acute myeloblastic leukemia cells (THP-1) and acute lymphoblastic leukemia (CCRF-CEM).Materials and methods. CBL0137 cytotoxicity was analyzed using the MTT test, the effects on the cell cycle and the induction of apoptosis was assessed by flow cytometry, the activity of signaling pathways in cells treated with CBL0137 was determined by real-time polymerase chain reaction.Results. Cell treatment with CBL0137 led to cell cycle arrest and apoptosis induction. In the study of CBL0137 effect on target gene clusters of 10 signal transduction pathways involved in the pathogenesis of acute leukemia we have showed that CBL0137 inhibited the expression of down-stream genes of WNT and Hedgehog signaling in both cell lines. In THP-1 cells we also observed the inhibition of the expression of PPARγ target and hypoxia-activated genes. In CCRF-CEM cells CBL0137 also induced the expression of Notch signaling target genes.Conclusion. The antitumor activity of CBL0137 was demonstrated on acute leukemia cell cultures, the drug possesses cytotoxicity, causes cell cycle arrest and activation of apoptosis. Significant changes in the expression of efferent gene clusters of several signaling pathways were observed in the cells treated with CBL0137.


Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3535
Author(s):  
Jen-Ying Hsu ◽  
Hui-Hsuan Lin ◽  
Ting-Shuan Li ◽  
Chaio-Yun Tseng ◽  
Yueching Wong ◽  
...  

Melanogenesis has many important physiological functions. However, abnormal melanin production causes various pigmentation disorders. Melanin synthesis is stimulated by α-melanocyte stimulating hormone (α-MSH) and ultraviolet (UV) irradiation. Lotus seedpod extract (LSE) has been reported as possessing antioxidative, anti-aging, and anticancer activities. The present study examined the effect of LSE on melanogenesis and the involved signaling pathways in vitro and in vivo. Results showed that non-cytotoxic doses of LSE and its main component epigallocatechin (EGC) reduced both tyrosinase activity and melanin production in the α-MSH-induced melanoma cells. Western blotting data revealed that LSE and EGC inhibited expressions of tyrosinase and tyrosinase-related protein 1 (TRP-1). Phosphorylation of p38 and protein kinase A (PKA) stimulated by α-MSH was efficiently blocked by LSE treatment. Furthermore, LSE suppressed the nuclear level of cAMP-response element binding protein (CREB) and disturbed the activation of melanocyte inducing transcription factor (MITF) in the α-MSH-stimulated B16F0 cells. The in vivo study revealed that LSE inhibited melanin production in the ear skin of C57BL/6 mice after exposure to UVB. These findings suggested that the anti-melanogenesis of LSE involved both PKA and p38 signaling pathways. LSE is a potent novo natural depigmenting agent for cosmetics or pharmaceutical applications.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Jing Chu ◽  
Yutong Li ◽  
Zhihai Deng ◽  
Zhenlin Zhang ◽  
Qun Xie ◽  
...  

Increasing evidence indicates that immunoglobulins are important for the regulation of various cancers including prostate cancer (PCa). However, the underlying mechanisms of IgG regulated PCa development remain to be further explored. Here, we demonstrated that IgG1 heavy chain (IGHG1) was increased in tissues from PCa patients. Inhibition of IGHG1 by antibody blocking or genetic knockdown suppressed cell growth and induced cell cycle arrest and ultimate apoptosis. Expression levels of c-Myc were positively correlated with the levels of IGHG1. Furthermore, MEK/ERK/c-Myc pathway lied downstream of IGHG1 in cultured prostate cancer cells. Inhibition of IGHG1 restrained the tumor growth in nude mice and inactivated MEK/ERK/c-Myc pathway both in vitro and in vivo. These findings suggest that IGHG1 play a crucial role during the development of prostate cancer and inhibition of IGHG1 may be a potential therapy in the treatment of PCa.


Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 382 ◽  
Author(s):  
Eunice Lozada-Delgado ◽  
Nilmary Grafals-Ruiz ◽  
Miguel Miranda-Román ◽  
Yasmarie Santana-Rivera ◽  
Fatma Valiyeva ◽  
...  

Glioblastoma (GBM) is the most common and aggressive of all brain tumors, with a median survival of only 14 months after initial diagnosis. Novel therapeutic approaches are an unmet need for GBM treatment. MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level. Several dysregulated miRNAs have been identified in all cancer types including GBM. In this study, we aimed to uncover the role of miR-143 in GBM cell lines, patient samples, and mouse models. Quantitative real-time RT-PCR of RNA extracted from formalin-fixed paraffin-embedded (FFPE) samples showed that the relative expression of miR-143 was higher in GBM patients compared to control individuals. Transient transfection of GBM cells with a miR-143 oligonucleotide inhibitor (miR-143-inh) resulted in reduced cell proliferation, increased apoptosis, and cell cycle arrest. SLC30A8, a glucose metabolism-related protein, was identified as a direct target of miR-143 in GBM cells. Moreover, multiple injections of GBM tumor-bearing mice with a miR-143-inh-liposomal formulation significantly reduced tumor growth compared to control mice. The reduced in vitro cell growth and in vivo tumor growth following miRNA-143 inhibition suggests that miR-143 is a potential therapeutic target for GBM therapy.


Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2455
Author(s):  
Eungyeong Jang ◽  
Jang-Hoon Lee

The flowering plant genus Alisma, which belongs to the family Alismataceae, comprises 11 species, including Alisma orientale, Alisma canaliculatum, and Alisma plantago-aquatica. Alismatis rhizome (Ze xie in Chinese, Takusha in Japanese, and Taeksa in Korean, AR), the tubers of medicinal plants from Alisma species, have long been used to treat inflammatory diseases, hyperlipidemia, diabetes, bacterial infection, edema, oliguria, diarrhea, and dizziness. Recent evidence has demonstrated that its extract showed pharmacological activities to effectively reverse cancer-related molecular targets. In particular, triterpenes naturally isolated from AR have been found to exhibit antitumor activity. This study aimed to describe the biological activities and plausible signaling cascades of AR and its main compounds in experimental models representing cancer-related physiology and pathology. Available in vitro and in vivo studies revealed that AR extract possesses anticancer activity against various cancer cells, and the efficacy might be attributed to the cytotoxic and antimetastatic effects of its alisol compounds, such as alisol A, alisol B, and alisol B 23-acetate. Several beneficial functions of triterpenoids found in AR might be due to p38 activation and inhibition of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways. Moreover, AR and its triterpenes inhibit the proliferation of cancer cells that are resistant to chemotherapy. Thus, AR and its triterpenes may play potential roles in tumor attack, as well as a therapeutic remedy alone and in combination with other chemotherapeutic drugs.


2019 ◽  
Vol 20 (12) ◽  
pp. 2865 ◽  
Author(s):  
Fawzia Al-blewi ◽  
Nadjet Rezki ◽  
Arshi Naqvi ◽  
Husna Qutb Uddin ◽  
Salsabeel Al-Sodies ◽  
...  

A focused array of green imidazolium ionic liquids (ILs) encompassing benzothiazole ring and amide linkage were designed and synthesized using quaternization and metathesis protocols. The synthesized ILs have been fully characterized by usual spectroscopic methods and screened for their anticancer activities against human cancer cell lines originating from breast and colon cancers. Collectively, our biological data demonstrate that the newly synthesized series has variable anticancer activities in the examined cancer types. The synthesized ILs 8, 10 and 21–29 comprising the methyl and methyl sulfonyl benzothiazole ring emerged as the most potent compounds with promising antiproliferative activities relative to their benzothiazole ring counterparts. Furthermore, the mechanism underlying the observed anticancer activity was investigated. The most active compound 22 appears to exert its anticancer effect through apoptosis dependent pathway in breast cancer cells. Interestingly, compound 22 has also shown good in silico absorption (81.75%) along with high gastro-intestinal absorption as per ADME predictions.


Plants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2124
Author(s):  
Cinzia Sanna ◽  
Arianna Marengo ◽  
Stefano Acquadro ◽  
Alessia Caredda ◽  
Roberta Lai ◽  
...  

In a search for natural compounds with anti-HIV-1 activity, we studied the effect of the ethanolic extract obtained from leaves, bark, and peels of Punica granatum L. for the inhibition of the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) and integrase (IN) LEDGF-dependent activities. The chemical analyses led to the detection of compounds belonging mainly to the phenolic and flavonoid chemical classes. Ellagic acid, flavones, and triterpenoid molecules were identified in leaves. The bark and peels were characterized by the presence of hydrolyzable tannins, such as punicalins and punicalagins, together with ellagic acid. Among the isolated compounds, the hydrolyzable tannins and ellagic acid showed a very high inhibition (IC50 values ranging from 0.12 to 1.4 µM and 0.065 to 0.09 µM of the RNase H and IN activities, respectively). Of the flavonoids, luteolin and apigenin were found to be able to inhibit RNase H and IN functions (IC50 values in the 3.7–22 μM range), whereas luteolin 7-O-glucoside showed selective activity for HIV-1 IN. In contrast, betulinic acid, ursolic acid, and oleanolic acid were selective for the HIV-1 RNase H activity. Our results strongly support the potential of non-edible P. granatum organs as a valuable source of anti-HIV-1 compounds.


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