Potential of Cytochrome P450, a Family of Xenobiotic Metabolizing Enzymes, in Cancer Therapy

Rg, Singh; Avadhesh, None; Sharma, Gaurav; Dholariya, Sagar; Shah, Rima; Goyal, Bela; Gupta, Subash C.

doi:10.1089/ars.2022.0116

Cited by 17 publications

(13 citation statements)

References 237 publications

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“…[16][17][18] Cytochrome P450 is an enzyme involved in the metabolism of phase 1 xenobiotics, toxins, and cancer drugs that can affect carcinogenesis, treatment outcomes, and cancer drug resistance. 19, 20 Chockley et al found that epithelial-mesenchymal transition (EMT)-induced modulation of E-cadherin levels and CADM1 overexpression could mediate increased tumor susceptibility to NK cytotoxicity, leading to inefficient metastasis. 21 From this, we hypothesize that CADM1 has multi-layered effects on regulating tumor cell proliferation, metastasis, and drug resistance.…”

Section: Discussionmentioning

confidence: 99%

Effect of CADM1 on TPF-induced chemotherapy in laryngeal squamous cell carcinoma

Nie

Li²,

Tan³

et al. 2023

J Int Med Res

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Objectives To explore the relationship between CADM1 expression and sensitivity to TPF-induced chemotherapy in laryngeal squamous cell carcinoma (LSCC) patients, then investigate its potential mechanisms. Methods Differential CADM1 expression was examined in chemotherapy-sensitive and chemotherapy-insensitive LSCC patient samples after TPF-induced chemotherapy using microarray analysis. Receiver operating characteristic (ROC) curve analysis and bioinformatics approaches were used to investigate the diagnostic value of CADM1. Small interfering RNAs (siRNAs) were used to knock down CADM1 expression in an LSCC cell line. Differential CADM1 expression was compared by qRT-PCR assays in 35 LSCC patients treated with chemotherapy, including 20 chemotherapy-sensitive and 15 chemotherapy-insensitive patients. Results Public database and primary patient data both suggest that CADM1 mRNA is expressed at lower levels in chemotherapy-insensitive LSCC samples, suggesting its potential usefulness as a biomarker. Knockdown of CADM1 with siRNAs led to decreased sensitivity of LSCC cells to TPF chemotherapy. Conclusions Upregulation of CADM1 expression can alter the sensitivity of LSCC tumors to TPF induction chemotherapy. CADM1 is a possible molecular marker and therapeutic target for induction chemotherapy in LSCC patients.

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Section: Discussionmentioning

confidence: 99%

Effect of CADM1 on TPF-induced chemotherapy in laryngeal squamous cell carcinoma

Nie

Li²,

Tan³

et al. 2023

J Int Med Res

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“…10,15 These enzymes actively participate in the metabolism and activation of numerous prodrugs, with their overexpression in cancer cells marking them as potential biomarkers for early-stage cancer diagnosis and monitoring therapeutic efficacy of cancer drugs. [16][17][18][19] Anticipating a surge in cancer cases, the World Health Organization predicts 24 million new cases and 14.4 million annual deaths by 2035. Early and accurate diagnosis, crucial for improving survival rates, hinges on detecting aberrant enzyme activity, which is directly linked to malignancies.…”

Section: Introductionmentioning

confidence: 99%

Real-time fluorescent monitoring of phase I xenobiotic-metabolizing enzymes

Iqbal,

Ilyas,

Akash

et al. 2024

RSC Adv.

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“…However, while clinical applications are mainly antimycotic, the mechanism of action involves inhibition of CYP450 [5,6], which plays a key role in several fundamental processes such as estrogen oxidation [7], control of metabolism and activity of many drugs [8], vitamin D metabolism [9], cell survival and proliferation [10]. A potential role of CYP450 has been suggested in several pathological conditions [11][12][13][14][15] and several cancer types [16][17][18][19][20][21][22][23][24][25][26], including melanoma [27]. This indicates how miconazole may affect several overlapping targets relevant in several pathological conditions, in addition to mycotic infections.…”

Section: Introductionmentioning

confidence: 99%

Anti-Melanoma Effects of Miconazole: Investigating the Mitochondria Involvement

Scatozza,

Giardina,

Valente

et al. 2024

IJMS

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Miconazole is an antimycotic drug showing anti-cancer effects in several cancers. However, little is known on its effects in melanoma. A375 and SK-MEL-28 human melanoma cell lines were exposed to miconazole and clotrimazole (up to 100 mM). Proliferation, viability with MTT assay and vascular mimicry were assayed at 24 h treatment. Molecular effects were measured at 6 h, namely, ATP-, ROS-release and mitochondria-related cytofluorescence. A metabolomic profile was also investigated at 6 h treatment. Carnitine was one of the most affected metabolites; therefore, the expression of 29 genes involved in carnitine metabolism was investigated in the public platform GEPIA2 on 461 melanoma patients and 558 controls. After 24 h treatments, miconazole and clotrimazole strongly and significantly inhibited proliferation in the presence of 10% serum on either melanoma cell lines; they also strongly reduced viability and vascular mimicry. After 6 h treatment, ATP reduction and ROS increase were observed, as well as a significant reduction in mitochondria-related fluorescence. Further, in A375, miconazole strongly and significantly altered expression of several metabolites including carnitines, phosphatidyl-cholines, all amino acids and several other small molecules, mostly metabolized in mitochondria. The expression of 12 genes involved in carnitine metabolism was found significantly modified in melanoma patients, 6 showing a significant impact on patients’ survival. Finally, miconazole antiproliferation activity on A375 was found completely abrogated in the presence of carnitine, supporting a specific role of carnitine in melanoma protection toward miconazole effect, and was significantly reversed in the presence of caspases inhibitors such as ZVAD-FMK and Ac-DEVD-CHO, and a clear pro-apoptotic effect was observed in miconazole-treated cells, by FACS analysis of Annexin V-FITC stained cells. Miconazole strongly affects proliferation and other biological features in two human melanoma cell lines, as well as mitochondria-related functions such as ATP- and ROS-release, and the expression of several metabolites is largely dependent on mitochondria function. Miconazole, likely acting via carnitine and mitochondria-dependent apoptosis, is therefore suggested as a candidate for further investigations in melanoma treatments.

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Potential of Cytochrome P450, a Family of Xenobiotic Metabolizing Enzymes, in Cancer Therapy

Cited by 17 publications

References 237 publications

Effect of CADM1 on TPF-induced chemotherapy in laryngeal squamous cell carcinoma

Effect of CADM1 on TPF-induced chemotherapy in laryngeal squamous cell carcinoma

Real-time fluorescent monitoring of phase I xenobiotic-metabolizing enzymes

Anti-Melanoma Effects of Miconazole: Investigating the Mitochondria Involvement

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