Re-Evaluation of Chemotherapeutic Potential of Pyoktanin Blue

Background: Very few papers covering the anticancer activity of azulenes have been reported, as compared with those of antibacterial and anti-inflammatory activity. This led us to investigate the antitumor potential of fifteen 4,6,8-trimethyl azulene amide derivatives against oral malignant cells. Methods: 4,6,8-Trimethyl azulene amide derivatives were newly synthesized. Anticancer activity was evaluated by tumor-specificity against four human oral squamous cell carcinoma (OSCC) cell lines over three normal oral cells. Neurotoxicity was evaluated by cytotoxicity against three neuronal cell lines over normal oral cells. Apoptosis induction was evaluated by Western blot and cell cycle analyses. Results: Among fifteen derivatives, compounds 7, 9, and 15 showed the highest anticancer activity, and relatively lower neurotoxicity than doxorubicin, 5-fluorouracil (5-FU), and melphalan. They induced the accumulation of a comparable amount of a subG1 population, but slightly lower extent of caspase activation, as compared with actinomycin D, used as an apoptosis inducer. The quantitative structure–activity relationship analysis suggests the significant correlation of tumor-specificity with a 3D shape of molecules, and possible involvement of inflammation and hormone receptor response pathways. Conclusions: Compounds 7 and 15 can be potential candidates of a lead compound for developing novel anticancer drugs.

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“…PSE was calculated by dividing the TS value by the CC 50 against tumor cells [ 15 , 29 ] [(D/B 2 ) × 100 and (C/A 2 ) × 100] ( Table 1 ).…”

Section: Methodsmentioning

confidence: 99%

Tumor-Specificity, Neurotoxicity, and Possible Involvement of the Nuclear Receptor Response Pathway of 4,6,8-Trimethyl Azulene Amide Derivatives

Naitoh

Orihara

Sakagami

et al. 2022

IJMS

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“…The induction of apoptosis in Ca9-22 cells was evaluated through morphological changes, and the Western blot and cell cycle analysis has been described previously [26]. In brief, cell morphology was checked periodically under the light microscope (EVOS FL, ThermoFisher Scientific, Waltham, MA, USA).…”

Section: Cytotoxicity Assaysmentioning

confidence: 99%

Cytotoxic Tumour-Selective 1,5-Diaryl-3-Oxo-1,4-Pentadienes Mounted on a Piperidine Ring

et al. 2021

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A series of 3,5-bis(benzylidene)-4-piperidones 2a–u were prepared as candidate cytotoxic agents. In general, the compounds are highly toxic to human gingival carcinoma (Ca9-22), human squamous carcinoma-2 (HSC-2) and human squamous carcinoma-4 (HSC-4) neoplasms, but less so towards non-malignant human gingival fibroblast (HGF), human periodontal ligament fibroblast (HPLF) and human pulp cells (HPC), thereby demonstrating tumour-selective toxicity. A further study revealed that most of the compounds in series 2 were more toxic to the human Colo-205 adenocarcinoma cell line (Colo-205), human HT29 colorectal adenocarcinoma cells (HT-29) and human CEM lymphoid cells (CEM) neoplasms than towards non-malignant human foreskin Hs27 fibroblast line (Hs27) cells. The potency of the cytotoxins towards the six malignant cell lines increased as the sigma and sigma star values of the aryl substituents rose. Attempts to condense various aryl aldehydes with 2,2,6,6-tetramethyl-4-piperidone led to the isolation of some 1,5-diaryl-1,4-pentadien-3-ones. The highest specificity for oral cancer cells was displayed by 2e and 2r. In the case of 2r, its selective toxicity exceeded that of doxorubicin and melphalan. The enones 2k, m, o have the highest SI values towards colon cancer and leukemic cells. Both 2e,r inhibited mitosis and increased the subG1 population (with a transient increase in G2/M phase cells). Slight activation of caspase-3, based on the cleavage of poly(ADP-ribose)polymerase (PARP) and procaspase 3, was detected.

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Comparison of UVC Sensitivity and Dectin-2 Expression Between Malignant and Non-malignant Cells

SHINDO

KUSANO

Sakagami

et al. 2022

In Vivo

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Background/Aim: Rapid spread of resulted in the revision of the value of ultraviolet C (UVC) sterilization in working spaces. This study aimed at investigating the UVC sensitivity of eighteen malignant and nonmalignant cell lines, the protective activity of sodium ascorbate against UVC, and whether Dectin-2 is involved in UVC sensitivity. Materials and Methods: Various cell lines were exposed to UVC for 3 min, and cell viability was determined using the MTT assay. Anti-UV activity was determined as the ratio of 50% cytotoxic concentration (determined with unirradiated cells) to 50% effective concentration (that restored half of the UV-induced loss of viability). Dectin-2 expression was quantified using flow cytometry. Results: The use of culture medium rather than phosphate-buffered saline is recommended as irradiation solution, since several cells are easily detached during irradiation in phosphate-buffered saline. Oral squamous cell carcinoma cell lines showed the highest UV sensitivity, followed by neuroblastoma, glioblastoma, leukemia, melanoma, lung carcinoma cells, and normal oral and dermal fibroblasts. Human dermal fibroblasts were more resistant than melanoma cell lines; however, both expressed Dectin-2. Sodium ascorbate at micromolar concentrations eliminated the cytotoxicity of UVC in these cell lines. Conclusion: Normal cells are generally UVC-resistant compared to corresponding malignant cells, which have higher growth potential. Dectin-2 protein expression itself may not be determinant of UVC sensitivity.In December 2019, several cases of pneumonia with unknown etiology emerged in Wuhan, China. From the throat swab sample of a patient, a novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) was identified, and the disease was named coronavirus disease 2019 (COVID-19) (1). Coronavirus infects the transbronchial and alveolar epithelial cells, inducing lung damages and other organ impairments (2). The COVID-19 disease causes psychological and physical complications (3).Environmental sodium hypochlorite cleaning and wearing masks effectively prevent infection of healthcare workers of hospitals, clinics, and schools. Also, the risk of infection in contaminated rooms can be reduced by disinfection with ultraviolet C (UVC) (4, 5). Intensive Care Units at the University Hospital use six 15 W low-vapor-pressure mercury lamps emitting 253.7 nm UVC [the average dose rate in the UVC cabinet was (2.7±0.5) mW/cm 2 ] (6). This value is about 27,000-fold higher than the effective and safe irradiation intensity for skin application (UVB: 0.1 μW/cm 2 ) (7). UVC disinfection lamps, which have strong bactericidal and virucidal power, have been solely used to improve indoor air quality in hospitals. Therefore, with increased time spent in such areas, their harmful effect on humans (such as skin cancer and cataract) may be augmented. If sterilization lamps are introduced at home, it would be necessary for us to protect ourselves from the injuring effects of UVC. It has been reported that Dectin...

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Re-Evaluation of Chemotherapeutic Potential of Pyoktanin Blue

Cited by 3 publications

References 36 publications

Tumor-Specificity, Neurotoxicity, and Possible Involvement of the Nuclear Receptor Response Pathway of 4,6,8-Trimethyl Azulene Amide Derivatives

Tumor-Specificity, Neurotoxicity, and Possible Involvement of the Nuclear Receptor Response Pathway of 4,6,8-Trimethyl Azulene Amide Derivatives

Cytotoxic Tumour-Selective 1,5-Diaryl-3-Oxo-1,4-Pentadienes Mounted on a Piperidine Ring

Comparison of UVC Sensitivity and Dectin-2 Expression Between Malignant and Non-malignant Cells

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