Platinum(IV) Complexes of trans-1,2-diamino-4-cyclohexene: Prodrugs Affording an Oxaliplatin Analogue that Overcomes Cancer Resistance

Six platinum(IV) compounds derived from an oxaliplatin analogue containing the unsaturated cyclic diamine trans-1,2-diamino-4-cyclohexene (DACHEX), in place of the 1,2-diaminocyclohexane, and a range of axial ligands, were synthesized and characterized. The derivatives with at least one axial chlorido ligand demonstrated solvent-assisted photoreduction. The electrochemical redox behavior was investigated by cyclic voltammetry; all compounds showed reduction potentials suitable for activation in vivo. X-ray photoelectron spectroscopy (XPS) data indicated an X-ray-induced surface reduction of the Pt(IV) substrates, which correlates with the reduction potentials measured by cyclic voltammetry. The cytotoxic activity was assessed in vitro on a panel of human cancer cell lines, also including oxaliplatin-resistant cancer cells, and compared with that of the reference compounds cisplatin and oxaliplatin; all IC50 values were remarkably lower than those elicited by cisplatin and somewhat lower than those of oxaliplatin. Compared to the other Pt(IV) compounds of the series, the bis-benzoate derivative was by far (5–8 times) the most cytotoxic showing that low reduction potential and high lipophilicity are essential for good cytotoxicity. Interestingly, all the complexes proved to be more active than cisplatin and oxaliplatin even in three-dimensional spheroids of A431 human cervical cancer cells.

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Antioxidant Stress and Anticancer of Peptide Chelate Selenium Element in vitro

10.21203/rs.3.rs-88931/v1 ◽

2020 ◽

Author(s):

Xian Li ◽

Xianjue Wang ◽

Gang Liu ◽

Yanan Xu ◽

Xinlin Wu ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Lines ◽

Photoelectron Spectroscopy ◽

Human Cancer ◽

Sulfhydryl Group ◽

Ultraviolet Absorption Spectrum ◽

Anticancer Activities ◽

X Ray ◽

Human Cancer Cell Lines

Abstract This contribution reports a facile synthesis of anticancer bioactive peptides (ACBP) - functionalized selenium particles (ACBP-S-Se) with enhanced anticancer activities and a detailed mechanistic evaluation of its regulation of oxidative stress in vitro. Structural and chemical characterizations were proved by ultraviolet absorption spectrum (UV), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), Nuclear magnetic resonance carbon (13C NMR) and hydrogen spectra (H NMR), scanning electron microscope (SEM), energy dispersive X-ray spectrom (EDX) and inductively coupled plasma mass spectrometry (ICP-MS). The results show that ACBP are effectively sulfhydrylation modification with S-acetylmercaptosuccinic anhydride (SAMSA) via chemical absorption. After the polypeptide was modified by sulfhydrylation, there were many sulfhydryl groups on the molecule, and the sulfhydryl group was used as the binding site of Se. A panel of selected human cancer cell lines demonstrated high susceptibility toward ACBP-S-Se and displayed significantly reduced proliferative abilities. Finally, the results presented herein suggest bioactive peptide chelate selenium element effectively inhibited the proliferation of MKN-45 and MKN-74 cell in vitro, which in turns allowed the successful application of the ACBP-S-Se in highly complex human cell lines. The related the regulation of oxidative stress gene is CDKN1A, CCNB1, TXN and MAP3K5, while CDKN1A and TXN have ability to protecting cells to reduce oxidative stress and promoting cell growth arrest. Therefore, the great potential exhibited by ACBP-S-Se could make them an ideal candidate as a chemotherapeutic agent for human cancers, especially for gastric cancer.

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A New Smoothened Antagonist Bearing the Purine Scaffold Shows Antitumour Activity In Vitro and In Vivo

International Journal of Molecular Sciences ◽

10.3390/ijms22168372 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8372

Author(s):

Ana María Zárate ◽

Christian Espinosa-Bustos ◽

Simón Guerrero ◽

Angélica Fierro ◽

Felipe Oyarzún-Ampuero ◽

...

Keyword(s):

Cancer Cells ◽

Human Cancer ◽

Antitumour Activity ◽

Anticancer Compounds ◽

Human Cancer Cells ◽

Cycle Arrest ◽

Apoptosis Inducer ◽

Purine Ring

The Smoothened (SMO) receptor is the most druggable target in the Hedgehog (HH) pathway for anticancer compounds. However, SMO antagonists such as vismodegib rapidly develop drug resistance. In this study, new SMO antagonists having the versatile purine ring as a scaffold were designed, synthesised, and biologically tested to provide an insight to their mechanism of action. Compound 4s was the most active and the best inhibitor of cell growth and selectively cytotoxic to cancer cells. 4s induced cell cycle arrest, apoptosis, a reduction in colony formation and downregulation of PTCH and GLI1 expression. BODIPY-cyclopamine displacement assays confirmed 4s is a SMO antagonist. In vivo, 4s strongly inhibited tumour relapse and metastasis of melanoma cells in mice. In vitro, 4s was more efficient than vismodegib to induce apoptosis in human cancer cells and that might be attributed to its dual ability to function as a SMO antagonist and apoptosis inducer.

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Overexpressed Pituitary Tumor-Transforming Gene Causes Aneuploidy in Live Human Cells

Endocrinology ◽

10.1210/en.2003-0305 ◽

2003 ◽

Vol 144 (11) ◽

pp. 4991-4998 ◽

Cited By ~ 76

Author(s):

Run Yu ◽

Wenge Lu ◽

Jiandong Chen ◽

Chris J. McCabe ◽

Shlomo Melmed

Keyword(s):

Cancer Cells ◽

Chromosome Segregation ◽

Pituitary Tumor ◽

Fluorescent Protein ◽

Human Cancer ◽

Live Cells ◽

Pituitary Tumor Transforming Gene ◽

Transforming Gene

Abstract The mammalian securin, pituitary tumor-transforming gene (PTTG), is overexpressed in several tumors and transforms cells in vitro and in vivo. To test the hypothesis that PTTG overexpression causes aneuploidy, enhanced green fluorescent protein (EGFP)-tagged PTTG (PTTG-EGFP) was expressed in human H1299 cancer cells (with undetectable endogenous PTTG expression) and mitosis of individual live cells observed. Untransfected cells and cells expressing EGFP alone exhibited appropriate mitosis. PTTG-EGFP markedly prolonged prophase and metaphase, indicating that PTTG blocks progression of mitosis to anaphase. In cells that underwent apparently normal mitosis (35 of 65 cells), PTTG-EGFP was degraded about 1 min before anaphase onset. Cells that failed to degrade PTTG-EGFP exhibited asymmetrical cytokinesis without chromosome segregation (18 of 65 cells) or chromosome decondensation without cytokinesis (9 of 65 cells), resulting in appearance of a macronucleus. Fifty-one of 55 cells expressing a nondegradable mutant PTTG exhibited asymmetrical cytokinesis without chromosome segregation, and some (4 of 55) decondensed chromosomes, both resulting in macronuclear formation. During this abnormal cytokinesis, all chromosomes and spindles and both centrosomes moved to one daughter cell, suggesting potential chaos in the subsequent mitosis. In conclusion, failure of PTTG degradation or enhanced PTTG accumulation, as a consequence of overexpression, inhibits mitosis progression and chromosome segregation but does not directly affect cytokinesis, resulting in aneuploidy. These results demonstrate that PTTG induces aneuploidy in single, live, human cancer cells.

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2, 3-Dihydro-3β-methoxy Withaferin-A Lacks Anti-Metastasis Potency: Bioinformatics and Experimental Evidences

Scientific Reports ◽

10.1038/s41598-019-53568-6 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Anupama Chaudhary ◽

Rajkumar S. Kalra ◽

Vidhi Malik ◽

Shashank P. Katiyar ◽

Durai Sundar ◽

...

Keyword(s):

Cell Migration ◽

Cancer Cells ◽

Cancer Cell ◽

Human Cancer ◽

Effector Proteins ◽

Withaferin A ◽

Migration And Invasion ◽

Cell Metastasis

AbstractWithaferin-A is a withanolide, predominantly present in Ashwagandha (Withania somnifera). It has been shown to possess anticancer activity in a variety of human cancer cells in vitro and in vivo. Molecular mechanism of such cytotoxicity has not yet been completely understood. Withaferin-A and Withanone were earlier shown to activate p53 tumor suppressor and oxidative stress pathways in cancer cells. 2,3-dihydro-3β-methoxy analogue of Withaferin-A (3βmWi-A) was shown to lack cytotoxicity and well tolerated at higher concentrations. It, on the other hand, protected normal cells against oxidative, chemical and UV stresses through induction of anti-stress and pro-survival signaling. We, in the present study, investigated the effect of Wi-A and 3βmWi-A on cell migration and metastasis signaling. Whereas Wi-A binds to vimentin and heterogeneous nuclear ribonucleoprotein K (hnRNP-K) with high efficacy and downregulates its effector proteins, MMPs and VEGF, involved in cancer cell metastasis, 3βmWi-A was ineffective. Consistently, Wi-A, and not 3βmWi-A, caused reduction in cytoskeleton proteins (Vimentin, N-Cadherin) and active protease (u-PA) that are essential for three key steps of cancer cell metastasis (EMT, increase in cell migration and invasion).

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Induction of apoptosis by in vitro and in vivo plant extracts derived from Menyanthes trifoliata L. in human cancer cells

Cytotechnology ◽

10.1007/s10616-018-0274-9 ◽

2019 ◽

Vol 71 (1) ◽

pp. 165-180 ◽

Cited By ~ 11

Author(s):

Tomasz Kowalczyk ◽

Przemysław Sitarek ◽

Ewa Skała ◽

Monika Toma ◽

Marzena Wielanek ◽

...

Keyword(s):

Cancer Cells ◽

Plant Extracts ◽

Human Cancer ◽

Human Cancer Cells ◽

Induction Of Apoptosis ◽

Menyanthes Trifoliata

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The effect of CELLFOODTM on radiotherapy or combined chemoradiotherapy: preclinical evidence

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835919878347 ◽

2019 ◽

Vol 11 ◽

pp. 175883591987834

Author(s):

Barbara Nuvoli ◽

Bruno Amadio ◽

Giancarlo Cortese ◽

Serena Benedetti ◽

Barbara Antoniani ◽

...

Keyword(s):

Cancer Cells ◽

Tumour Growth ◽

Human Cancer ◽

Combined Treatment ◽

Treatment Strategies ◽

Phosphoglycerate Kinase ◽

Immunohistochemical Analysis ◽

Chemotherapy Treatment ◽

Human Cancer Cell Lines

Background: Based on previous observations that the nutraceutical CELLFOOD™ (CF), the ‘physiological modulator’ that aimed to make oxygen available ‘on demand’, inhibits the growth of cancer cells, this study was designed to investigate the role of CF in the regulation of hypoxia-inducible factor 1 alpha (HIF1α) and its correlated proteins, phosphoglycerate kinase 1 and vascular endothelial growth factor. Our idea was that CF, acting on HIF1α, in combination with current anticancer therapies could improve their effectiveness. Methods: To evaluate the effect of CF in association with radiotherapy and chemotherapy, different human cancer cell lines and mice with mesothelioma were analysed by tumour growth, clonogenic assay, western blot and immunohistochemical analysis. Results: CF in combination with radiation with or without cisplatin increases the death rate of cancer cells. In vivo, 70% of mice treated with CF before the mesothelioma graft did not show any tumour growth, indicating a possible preventive effect of CF. Moreover, in mouse mesothelioma xenografts, CF improves the effect of radiotherapy also in combination with chemotherapy treatment. Immunohistochemical analysis of tumour explants showed that HIF1α expression was reduced by the combination of CF and radiotherapy treatment and even more by the combination of CF and radiotherapy and chemotherapy treatment. Mechanistically, CF increases the fraction of oxygenated cells, making the radiotherapy more effective with a greater production of reactive oxygen species (ROS) that in turn, reduce the HIF1α expression. This effect is amplified by further increase in ROS from chemotherapy. Conclusions: Collectively, results from preclinical trials suggest that CF could be a useful intervention to improve the efficacy of radiotherapy or combined treatment strategies and could be a promising treatment modality to counteract cancer.

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Positive interactions between human interferon and cepharanthin against human cancer cells in vitro and in vivo

Cancer Chemotherapy and Pharmacology ◽

10.1007/bf00686278 ◽

1994 ◽

Vol 35 (1) ◽

pp. 10-16 ◽

Cited By ~ 8

Author(s):

Minoru Ono ◽

Noriaki Tanaka ◽

Kunzo Orita

Keyword(s):

Cancer Cells ◽

Human Cancer ◽

Human Interferon ◽

Positive Interactions ◽

Human Cancer Cells

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In vitro photodynamic treatment of cancer cells induced by aza-BODIPYs

Photochemical & Photobiological Sciences ◽

10.1039/d0pp00026d ◽

2020 ◽

Vol 19 (6) ◽

pp. 790-799

Author(s):

Miryam Chiara Malacarne ◽

Stefano Banfi ◽

Enrico Caruso

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Iodine Atom ◽

Human Cancer ◽

Cancer Cell Lines ◽

Human Cancer Cell ◽

Photodynamic Treatment ◽

Human Cancer Cell Lines

Two new aza-BODIPY photosensitizers featuring an iodine atom on each pyrrolic unit of their structure, were synthesized in fairly good yields and tested in vitro on two human cancer cell lines to assess their photodynamic efficacy.

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