Topical Application of Houttuynia Cordata Thunb Ethanol Extracts Increases Tumor Infiltrating CD8+/Treg Cells Ratio and Inhibits Cutaneous Squamous Cell Carcinoma In Vivo

Abstract Houttuynia cordata Thunb (HCT) is a medicinal and edible herb which has beneficial effects on various diseases due to its diuretic, anti-inflammatory, anti-oxidative, anti-microbial, anti-viral, anti-cancer and anti-diabetic properties. Most of reports of its anti-cancer activity were conducted in vitro, and its effects on cutaneous squamous cell carcinoma (SCC) has not been investigated yet. Using DMBA/TPA induced SCC mice model, we found that topical treatment by HCT, as well as its bioactive ingredient monomer, efficiently inhibited tumor growth. Mechanistically, we found tumor infiltrating CD4+, Foxp3+ T regulatory cells (Tregs) were significantly reduced and CD8+/Treg cells ratio was largely increased in tumors after HCT treatment. In addition, several chemokines which recruited immune cells were largely reduced when SCC cancer cells were treated by HCT in vitro. Our results demonstrate the therapeutic effects of HCT on cutaneous SCC and indicate it might inhibit cancer through regulating tumor infiltrating lymphocytes and the tumor immune microenvironments.

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P5. Anti-cancer effects of cordycepin on oral squamous cell carcinoma proliferation and apoptosis in vitro

Oral Oncology ◽

10.1016/j.oraloncology.2011.06.248 ◽

2011 ◽

Vol 47 ◽

pp. S75

Author(s):

J.-H. Lee ◽

J.-Y. Yoon ◽

H. Myoung ◽

S.-M. Hong ◽

S.-M. Kim ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Anti Cancer ◽

Proliferation And Apoptosis

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A Unique Panel of Patient-Derived Cutaneous Squamous Cell Carcinoma Cell Lines Provides a Preclinical Pathway for Therapeutic Testing

International Journal of Molecular Sciences ◽

10.3390/ijms20143428 ◽

2019 ◽

Vol 20 (14) ◽

pp. 3428 ◽

Cited By ~ 5

Author(s):

Sakinah Hassan ◽

Karin J. Purdie ◽

Jun Wang ◽

Catherine A. Harwood ◽

Charlotte M. Proby ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Cell Lines ◽

Squamous Cell ◽

Drug Screening ◽

Cutaneous Squamous Cell Carcinoma ◽

Model Systems ◽

Screening Methods

Background: Cutaneous squamous cell carcinoma (cSCC) incidence continues to rise with increasing morbidity and mortality, with limited treatment options for advanced disease. Future improvements in targeted therapy will rely on advances in genomic/transcriptomic understanding and the use of model systems for basic research. We describe here the panel of 16 primary and metastatic cSCC cell lines developed and characterised over the past three decades in our laboratory in order to provide such a resource for future preclinical research and drug screening. Methods: Primary keratinocytes were isolated from cSCC tumours and metastases, and cell lines were established. These were characterised using short tandem repeat (STR) profiling and genotyped by whole exome sequencing. Multiple in vitro assays were performed to document their morphology, growth characteristics, migration and invasion characteristics, and in vivo xenograft growth. Results: STR profiles of the cSCC lines allow the confirmation of their unique identity. Phylogenetic trees derived from exome sequence analysis of the matched primary and metastatic lines provide insight into the genetic basis of disease progression. The results of in vivo and in vitro analyses allow researchers to select suitable cell lines for specific experimentation. Conclusions: There are few well-characterised cSCC lines available for widespread preclinical experimentation and drug screening. The described cSCC cell line panel provides a critical tool for in vitro and in vivo experimentation.

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Abstract A248: Therapeutic effects of the dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor PF-04691502 on in vitro and in vivo models of head and neck squamous cell carcinoma.

10.1158/1535-7163.targ-11-a248 ◽

2011 ◽

Author(s):

Amanda Herzog ◽

Yansong Bian ◽

Bradford Hall ◽

Jamie Coupar ◽

Julie Kan ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Mammalian Target Of Rapamycin ◽

Therapeutic Effects ◽

In Vivo Models ◽

Phosphoinositide 3 Kinase

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Reduction in cisplatin genotoxicity (micronucleus formation) in non target cells of mice by protransfersome gel formulation used for management of cutaneous squamous cell carcinoma

Acta Pharmaceutica ◽

10.2478/v10007-011-0004-8 ◽

2011 ◽

Vol 61 (1) ◽

pp. 63-71 ◽

Cited By ~ 12

Author(s):

Vandana Gupta ◽

Ramesh Agrawal ◽

Piyush Trivedi

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Skin Permeation ◽

Research Work ◽

Cutaneous Squamous Cell Carcinoma ◽

Histopathological Study ◽

Target Cells ◽

Micronucleus Formation

Reduction in cisplatin genotoxicity (micronucleus formation) in non target cells of mice by protransfersome gel formulation used for management of cutaneous squamous cell carcinomaCisplatin-loaded protransfersome system was prepared and characterized forin vitrodrug permeation, drug deposition and antitumor effect. A histopathological study and a genotoxicity study were also done. The skin permeation data of cisplatin from protransfersome gel formulation revealed 494.33 ± 11.87 μg cm-2, which was significantly higher than that from the control plain drug solution in 0.9 % NaCl (p< 0.001). Untreated group of animals showed invasive moderately differentiated keratinizing squamous cell carcinoma (malignant stage). However, with cisplatin loaded protransfersome gel system simple epithelial hyperplasia (pre-cancerous stage) with no cancerous growth was observed. Also, a significant induction in micronucleus formation was found in the group that was treated with injectable intraperitoneal cisplatin preparation in 0.9 % saline as compared to the group treated with topical protransfersome gel formulation. The findings of this research work appear to support improved, site-specific and localized drug action in the skin, thus providing a better option for dealing with skin related problems like squamous cell carcinoma.

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Repression of BET activity sensitizes oral squamous cell carcinoma to PARP inhibition via inhibiting DNA homologous recombination and immune inhibition

10.21203/rs.3.rs-26946/v2 ◽

2021 ◽

Author(s):

Dongdong Tong ◽

Xin Zhang ◽

Fenghe Zhang ◽

xiaojing Liu

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Parp Inhibitor ◽

Cell Cycle Distribution ◽

Bet Inhibitor ◽

Anti Cancer

Abstract Objective: To investigate the therapeutic resistance mechanism of oral squamous cell carcinoma (OSCC) to the PARP inhibitor olaparib and explore the combination with the BET inhibitor JQ1 to enhance its treatment effects. Material and Methods: Cell proliferation, apoptosis and cell cycle distribution were evaluated. Levels of relevant factors were determined by quantitative real-time PCR, western blot and immunofluorescence. The effect of the combination treatment on xenograft OSCC mouse model was examined.Results: Cal27 cells were more sensitive to the PARP inhibitor olaparib than Scc25 cells. Functional assays demonstrated that olaparib induced HR repair and upregulated PD-L1 expression, which results in drug resistance of OSCC to olaparib. Variations of these factors in the two cell lines may explain different sensitivity to olaparib. Moreover, the JQ1 BET inhibitor and olaparib synergistically exhibited anti-cancer effects in OSCC in vitro and in vivo and inhibited essential HR repair factors RAD51, BRCA1, and TOPBP1 through the ATR/CHK1 pathway and immune suppression mediated by the PD-L1 pathway.Conclusions: Elevated HR and PD-L1 are involved in resistance mechanisms of OSCC to olaparib, attenuating its anti-tumor effects. Our results suggest that the strong synergistic anti-cancer effects of the combination of olaparib with the JQ1 BET inhibitor in OSCC in vitro and in vivo may be via suppression of the ATR/CHK1-mediated DNA damage response and PD-L1-related immune escape, indicating this combination strategy as a possible therapeutic approach for OSCC.

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Folic acid mediated cisplatin magnetic nanodrug targeting in the treatment of oral squamous cell carcinoma

Materials Express ◽

10.1166/mex.2021.2036 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1299-1305

Author(s):

Xiangyong Cheng ◽

Lan Zhang ◽

Xiqing Liu ◽

Liangpeng Xu ◽

Junjie Liu

Keyword(s):

Squamous Cell Carcinoma ◽

Folic Acid ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Malignant Tumors ◽

Specific Cell ◽

Therapeutic Effects

Cisplatin, a non-specific cell cycle antineoplastic drug, has therapeutic effects on a variety of malignant tumors. However, cisplatin has some drawbacks, such as poor targeting, which can lead to damage in normal tissue adjacent to a cancer, causing serious side effects in patients. In this study, we designed and developed a folic acid (FA)-mediated cisplatin magnetic nanodrug, FA-CDDP-MNPs, and investigated its efficacy in the treatment of oral squamous cell carcinoma (OSCC). In vitro and in vivo experiments showed that FA-CDDP-MNPs had a greater inhibitory effect on OSCC than CDDP alone. Due to the introduction of FA, the targeting of FA-CDDPMNPs was improved, and its cytotoxicity reduced. The successful design and development of FA-CDDP-MNPs provides a basis for novel drug development and design in the future.

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Clinicopathological roles of S100A8 and S100A9 in cutaneous squamous cell carcinoma in vivo and in vitro

Archives of Dermatological Research ◽

10.1007/s00403-014-1453-y ◽

2014 ◽

Vol 306 (5) ◽

pp. 489-496 ◽

Cited By ~ 15

Author(s):

Dae-Kyoung Choi ◽

Zheng Jun Li ◽

In-Kyu Chang ◽

Min-Kyung Yeo ◽

Jin-Man Kim ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cutaneous Squamous Cell Carcinoma

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miR-22 promotes stem cell traits via activating Wnt/β-catenin signaling in cutaneous squamous cell carcinoma

Oncogene ◽

10.1038/s41388-021-01973-5 ◽

2021 ◽

Author(s):

Shukai Yuan ◽

Peitao Zhang ◽

Liqi Wen ◽

Shikai Jia ◽

Yufan Wu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cancer Metastasis ◽

Cutaneous Squamous Cell Carcinoma ◽

Chemotherapy Sensitivity ◽

Oncogenic Pathways ◽

Chemically Induced ◽

Xenograft Mice

AbstractEmerging evidence suggests that the cancer stem cells (CSCs) are key culprits of cancer metastasis and drug resistance. Understanding mechanisms regulating the critical oncogenic pathways and CSCs function could reveal new diagnostic and therapeutic strategies. We now report that miR-22, a miRNA critical for hair follicle stem/progenitor cell differentiation, promotes tumor initiation, progression, and metastasis by maintaining Wnt/β-catenin signaling and CSCs function. Mechanistically, we find that miR-22 facilitates β-catenin stabilization through directly repressing citrullinase PAD2. Moreover, miR-22 also relieves DKK1-mediated repression of Wnt/β-catenin signaling by targeting a FosB-DDK1 transcriptional axis. miR-22 knockout mice showed attenuated Wnt/β-catenin activity and Lgr5+ CSCs penetrance, resulting in reduced occurrence, progression, and metastasis of chemically induced cutaneous squamous cell carcinoma (cSCC). Clinically, miR-22 is abundantly expressed in human cSCC. Its expression is even further elevated in the CSCs proportion, which negatively correlates with PAD2 and FosB expression. Inhibition of miR-22 markedly suppressed cSCC progression and increased chemotherapy sensitivity in vitro and in xenograft mice. Together, our results revealed a novel miR-22-WNT-CSCs regulatory mechanism in cSCC and highlight the important clinical application prospects of miR-22, a common target molecule for Wnt/β-catenin signaling and CSCs, for patient stratification and therapeutic intervention.

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