The in vitro apoptotic effect of new zinc complex possessing folic acid and phenanthroline on cervix cancer cells

High-risk human papilloma virus (HPV) infection is directly associated with cervical cancer development. Arsenic trioxide (ATO), despite inducing apoptosis in HPV-infected cervical cancer cells in vitro, has been compromised by toxicity and poor pharmacokinetics in clinical trials. Therefore, to improve ATO’s therapeutic profile for HPV-related cancers, this study aims to explore the effects of length of ligand spacers of folate-targeted liposomes on the efficiency of ATO delivery to HPV-infected cells. Fluorescent ATO encapsulated liposomes with folic acid (FA) conjugated to two different PEG lengths (2000 Da and 5000 Da) were synthesised, and their cellular uptake was examined for HPV-positive HeLa and KB and HPV-negative HT-3 cells using confocal microscopy, flow cytometry, and spectrophotometer readings. Cellular arsenic quantification and anti-tumour efficacy was evaluated through inductively coupled plasma-mass spectrometry (ICP-MS) and cytotoxicity studies, respectively. Results showed that liposomes with a longer folic acid-polyethylene glycol (FA-PEG) spacer (5000 Da) displayed a higher efficiency in targeting folate receptor (FR) + HPV-infected cells without increasing any inherent cytotoxicity. Targeted liposomally delivered ATO also displayed superior selectivity and efficiency in inducing higher cell apoptosis in HPV-positive cells per unit of arsenic taken up than free ATO, in contrast to HT-3. These findings may hold promise in improving the management of HPV-associated cancers.

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In vitro apoptotic effect of cassaine-type diterpene amides from Erythrophleum fordii on PC-3 prostate cancer cells

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2014.09.025 ◽

2014 ◽

Vol 24 (21) ◽

pp. 4989-4994 ◽

Cited By ~ 7

Author(s):

Tran Manh Hung ◽

To Dao Cuong ◽

Jeong Ah Kim ◽

Jeong Hyung Lee ◽

Mi Hee Woo ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Prostate Cancer Cells ◽

Apoptotic Effect ◽

Erythrophleum Fordii

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Folate Receptor-Mediated Cancer Cell Specific Gene Delivery Using Folic Acid-Conjugated Oligochitosans

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2006.465 ◽

2006 ◽

Vol 6 (9) ◽

pp. 2860-2866 ◽

Cited By ~ 53

Author(s):

Dongwon Lee ◽

Richard Lockey ◽

Shyam Mohapatra

Keyword(s):

Folic Acid ◽

Gene Transfer ◽

Gene Delivery ◽

Cancer Cells ◽

Transfection Efficiency ◽

Folate Receptor ◽

Weight Ratio ◽

Specific Gene ◽

Transfer Potential

Chitosan-mediated gene delivery has gained an increasing interest due to its ability to treat cancers and genetic diseases. However, low transfection efficiency and lack of target specificity limit its application for gene and drug delivery. In the present work, folic acid was covalently conjugated to chitosan as a targeting ligand in an attempt to specifically deliver DNA to folate receptor-overexpressing cancer cells. Folic acid-conjugated chitosan (FACN) was successfully synthesized and characterized by 1H-NMR and is biocompatible. In vitro gene transfer potential of FACN was evaluated in human epithelial ovarian cancer OV2008 cells and human breast cancer MCF-7 cells. FACN at a weight ratio of 10 : 1 exhibited significantly (< 0.01) enhanced gene transfer potential in folate receptor-overexpressing cancer cells as compared to unmodified chitosan. Transfection of FACN/pDNA nanocomplexes is competitively inhibited by free folic acid, suggesting the specific gene delivery of FACN/pDNA nanocomplexes is achieved through folate receptor-mediated endocytosis. Taken together, these results demonstrate that FACN provides a promising carrier for cancer gene therapy.

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Homocysteine induces melanocytes apoptosis via PERK–eIF2α–CHOP pathway in vitiligo

Clinical Science ◽

10.1042/cs20200218 ◽

2020 ◽

Vol 134 (10) ◽

pp. 1127-1141 ◽

Cited By ~ 1

Author(s):

Jiaxi Chen ◽

Tongtian Zhuang ◽

Jianru Chen ◽

Yangzi Tian ◽

Xiuli Yi ◽

...

Keyword(s):

Folic Acid ◽

Stress Protein ◽

Folic Acid Supplementation ◽

Translation Initiation Factor ◽

Initiation Factor ◽

Eukaryotic Translation ◽

Homologous Protein ◽

Apoptotic Effect ◽

Induced Apoptosis

Abstract Vitiligo is a depigmentation disorder that develops as a result of the progressive disappearance of epidermal melanocytes. The elevated level of amino acid metabolite homocysteine (Hcy) has been identified as circulating marker of oxidative stress and known as a risk factor for vitiligo. However, the mechanism underlying Hcy-regulated melanocytic destruction is currently unknown. The present study aims to elucidate the effect of Hcy on melanocytic destruction and its involvement in the pathogenesis of vitiligo. Our results showed that Hcy level was significantly elevated in the serum of progressive vitiligo patients. Notably, Hcy induced cell apoptosis in melanocytes via activating reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress protein kinase RNA-like ER kinase (PERK)–eukaryotic translation initiation factor 2α (eIF2α)–C/EBP homologous protein (CHOP) pathway. More importantly, folic acid, functioning in the transformation of Hcy, could lower the intracellular Hcy level and further reverse the apoptotic effect of Hcy on melanocytes. Additionally, Hcy disrupted melanogenesis whereas folic acid supplementation could reverse the melanogenesis defect induced by Hcy in melanocytes. Taken together, Hcy is highly increased in vitiligo patients at progressive stage, and our in vitro studies revealed that folic acid could protect melanocytes from Hcy-induced apoptosis and melanin synthesis inhibition, indicating folic acid as a potential benefit agent for patients with progressive vitiligo.

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Multifunctional Nanoplatform for Targeted Laser-induced Hyperthermia and Microscopy of Breast Cancer Cells using SPION-based Gold and Folic Acid Conjugated Nanodendrimers: An in vitro Assay

Journal of Nanomedicine & Nanotechnology ◽

10.4172/2157-7439.1000432 ◽

2017 ◽

Vol 08 (02) ◽

Author(s):

Khosroshahi ME ◽

Tajabadi M

Keyword(s):

Breast Cancer ◽

Folic Acid ◽

Cancer Cells ◽

Breast Cancer Cells ◽

In Vitro Assay ◽

Vitro Assay ◽

Induced Hyperthermia

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Folic acid-functionalized niosomal nanoparticles for selective dual-drug delivery into breast cancer cells: An in-vitro investigation

Advanced Powder Technology ◽

10.1016/j.apt.2020.08.011 ◽

2020 ◽

Vol 31 (9) ◽

pp. 4064-4071

Author(s):

Iman Akbarzadeh ◽

Mohammad Tavakkoli Yaraki ◽

Saeedeh Ahmadi ◽

Mohsen Chiani ◽

Dariush Nourouzian

Keyword(s):

Breast Cancer ◽

Drug Delivery ◽

Folic Acid ◽

Cancer Cells ◽

Breast Cancer Cells ◽

In Vitro Investigation ◽

Dual Drug

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Mediation of HER2 expression-dependent antiproliferative and pro-apoptotic effect of pan-HER2-specific TKIs on breast cancer cells through STAT5 and JNK.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e11606 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e11606-e11606

Author(s):

Daphne Gschwantler-Kaulich

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Breast Cancer Cells ◽

Her2 Expression ◽

Her Family ◽

Proliferation And Apoptosis ◽

Apoptotic Effect

e11606 Background: HER-targeted tyrosine kinase inhibitors (TKIs) have demonstrated pro-apoptotic and antiproliferative effects in vitro and in vivo. The exact pathways through which TKIs exert their antineoplastic effects are, however, still not completely understood. Methods: Using Milliplex assays, we have investigated the effects of the three panHER-TKIs lapatinib, canertinib and afatinib on signal transduction cascade activation in SKBR3, T47D and Jurkat neoplastic cell lines. The growth-inhibitory effect of blockade of HER and of JNK and STAT5 signaling was measured by proliferation- and apoptosis-assays using formazan dye labeling of viable cells, Western blotting for cleaved PARP and immunolabeling for active caspase 3, respectively. Results: All three HER-TKIs clearly inhibited proliferation and increased apoptosis in HER2 overexpressing SKBR3 cells, while their effect was less pronounced on HER2 moderately expressing T47D cells where they exerted only a weak antiproliferative and essentially no pro-apoptotic effect. Remarkably, phosphorylation/activation of JNK and STAT5A/B were inhibited by HER-TKIs only in the sensitive, but not in the resistant cells. In contrast, phosphorylation/activation of ERK/MAPK, STAT3, CREB, p70 S6 kinase, IkBa, and p38 were equally affected by HER-TKIs in both cell lines, irrespective of their sensitivity against the HER-TKIs. Moreover, we demonstrated that direct pharmacological blockade of JNK and STAT5 abrogates cell growth in both HER-TKI-sensitive as well as -resistant breast cancer cells, respectively. Conclusions: We have shown that HER-TKIs exert a HER2 expression-dependent effect on proliferation and apoptosis in cancer cell lines in vitro, which is at least partially mediated by blockade of JNK and STAT5A/B. Despite slight differences in their specificity towards individual members of the HER family all three inhibitors had comparable antiproliferative and proapoptotic effects in vitro.

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PEGylated-folic acid–modified black phosphorus quantum dots as near-infrared agents for dual-modality imaging-guided selective cancer cell destruction

Nanophotonics ◽

10.1515/nanoph-2019-0506 ◽

2020 ◽

Vol 9 (8) ◽

pp. 2425-2435 ◽

Cited By ~ 3

Author(s):

Jing Wang ◽

Dong Liang ◽

Zehua Qu ◽

Ivan M. Kislyakov ◽

Valery M. Kiselev ◽

...

Keyword(s):

Quantum Dots ◽

Folic Acid ◽

Cancer Cells ◽

Near Infrared ◽

Processing System ◽

Black Phosphorus ◽

Optical Absorbance ◽

Present Design ◽

Black Phosphorus Quantum Dots

AbstractBiological systems have high transparence to 700–1100-nm near-infrared (NIR) light. Black phosphorus quantum dots (BPQDs) have high optical absorbance in this spectrum. This optical property of BPQDs integrates both diagnostic and therapeutic functions together in an all-in-one processing system in cancer theranostic approaches. In the present study, BPQDs were synthesized and functionalized by targeting moieties (PEG-NH2-FA) and were further loaded with anticancer drugs (doxorubicin) for photodynamic–photothermal–chemotherapy. The precise killing of cancer cells was achieved by linking BPQDs with folate moiety (folic acid), internalizing BPQDs inside cancer cells with folate receptors and NIR triggering, without affecting the receptor-free cells. These in vitro experiments confirm that the agent exhibited an efficient photokilling effect and a light-triggered and heat-induced drug delivery at the precise tumor sites. Furthermore, the nanoplatform has good biocompatibility and effectively obliterates tumors in nude mice, showing no noticeable damages to noncancer tissues. Importantly, this nanoplatform can inhibit tumor growth through visualized synergistic treatment and photoacoustic and photothermal imaging. The present design of versatile nanoplatforms can allow for the adjustment of nanoplatforms for good treatment efficacy and multiplexed imaging, providing an innovation for targeted tumor treatment.

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