Caspase-3 expression in normal oral epithelium, oral submucous fibrosis and oral squamous cell carcinoma

Veeravarmal, Veeran; Austin, Ravi David; Siddavaram, Nagini; Thiruneelakandan, Sambanthan; Nassar, Mohamed Hanifa Mohamed

doi:10.4103/0973-029x.190947

Cited by 20 publications

(28 citation statements)

References 17 publications

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“…This inhibition would permit an uncontrolled proliferation of keratinocytes with damaged DNA, whose tumorigenic mutations could lead to the oral cancer development. The reduced expression of caspase 3 in oral cancer tissues has been related to malignant transformation 34 . A recent investigation demonstrated that norepinephrine protected against apoptosis of mesenchymal stem cells by inhibiting the expression of caspase 3 via AKT/BCL-2 11 .…”

Section: Discussionmentioning

confidence: 99%

Stress hormones promote DNA damage in human oral keratinocytes

Valente

Cardoso

Kayahara

et al. 2021

Sci Rep

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Chronic stress increases the systemic levels of stress hormones norepinephrine and cortisol. As well as tobacco-specific carcinogen NNK (4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone), they can induce expressive DNA damage contributing to the cancer development. However, it is unknown whether stress hormones have genotoxic effects in oral keratinocytes. This study investigated the effects of stress hormones on DNA damage in a human oral keratinocyte cell line (NOK-SI). NOK-SI cells stimulated with norepinephrine or cortisol showed higher DNA damage compared to untreated cells. Norepinephrine-induced DNA damage was reversed by pre-treatment with beta-adrenergic blocker propranolol. Cells treated with NNK combined to norepinephrine displayed reduced levels of caspases 3 and 7. Cortisol also reduced the activity of pro-apoptotic enzymes. NNK or norepinephrine promoted single-strand breaks and alkali-label side breaks in the DNA of NOK-SI cells. Pre-treatment of cells with propranolol abolished these effects. Carcinogen NNK in the presence or absence of cortisol also induced DNA damage of these cells. The genotoxic effects of cortisol alone and hormone combined with NNK were blocked partially and totally, respectively, by the glucocorticoid receptor antagonist RU486. DNA damage promoted by NNK or cortisol and carcinogen combined to the hormone led to intracellular γH2AX accumulation. The effects caused by NNK and cortisol were reversed by propranolol and glucocorticoid receptor antagonist RU486, respectively. Propranolol inhibited the oxidation of basis induced by NNK in the presence of DNA-formamidopyrimidine glycosylase. DNA breaks induced by norepinephrine in the presence or absence of NNK resulted in higher 8OHdG cellular levels. This effect was also induced through beta-adrenergic receptors. Together, these findings indicate that stress hormones induce DNA damage of oral keratinocytes and could contribute to oral carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Stress hormones promote DNA damage in human oral keratinocytes

Valente

Cardoso

Kayahara

et al. 2021

Sci Rep

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“…Overexpression of caspase 3 in oral carcinoma might be due to enhance or promote the apoptotic cascade. (Veeravarmal et al, 2016) reported low or absence of caspase 3 expression in oral squamous cell carcinoma. They suggested that caspase 3 expression tends to be decreased as the tumour progress.…”

Section: Resultsmentioning

confidence: 99%

Myrtenal averts apoptotic evasion of cancer cells in 7,12-dimethylbenz(a)anthracene induced experimental oral carcinogenesis

Buddhan

Manoharan

Muralinaidu

2020

ijrps

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Apoptotic avoidance is one of the foremost characteristic features of tumour cells. Apoptotic induction in cancer cells could thus help to identify new anticancer agents from the natural products. The present study has taken an effort to investigate the apoptotic efficacy of myrtenal, a monoterpene, in 7,12-dimethylbenz(a)anthracene (DMBA) induced oral carcinoma in male golden Syrian hamsters. The present study used the potent carcinogen, 7,12- dimethylbenz(a)anthracene, to develop oral tumours in the buccal pouches of the golden Syrian hamsters. Topical application of the above said carcinogen on the buccal mucosa (3 times a week for 14 weeks) resulted in well differentiated oral squamous cell carcinoma. The apoptotic potential of myrtenal was investigated using a spectrum of apoptotic markers, including pro-apoptotic and anti-apoptotic markers. Oral tumours developed in the buccal mucosa of hamsters showed higher expression of mutant p53 protein, Bcl-2 and lowered expression of Bax, Bad, Bid, caspase 3 and caspase 9. Myrtenal treatment at a dose of 230mg/kg bw orally to the hamsters treated with DMBA modulated the above said apoptotic markers towards tumour suppression or inhibition. The present findings thus suggests that the tumour preventive effect of myrtenal could partly be ascribed to its apoptotic induction potential during DMBA induced oral carcinogenesis.

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“… 101 Stromal hypoxia leading to caspase-3 and -9 activation is the most plausible explanation for the downregulation of K-19 and the appearance of CYFRA21-1 in OSF. 102 , 103 CYFRA21-1 is thus a promising noninvasive proxy marker of hypoxia-initiated epithelial apoptosis and atrophy in OSF patients (Fig. 5a ).…”

Section: Alterations In the Expression Pattern Of Om-scms In Osf Opmmentioning

confidence: 99%

Loss of oral mucosal stem cell markers in oral submucous fibrosis and their reactivation in malignant transformation

Sharma¹,

Fonseca

Hunter

et al. 2020

Int J Oral Sci

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The integrity of the basal stem cell layer is critical for epithelial homoeostasis. In this paper, we review the expression of oral mucosal stem cell markers (OM-SCMs) in oral submucous fibrosis (OSF), oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) to understand the role of basal cells in potentiating cancer stem cell behaviour in OSF. While the loss of basal cell clonogenicity triggers epithelial atrophy in OSF, the transition of the epithelium from atrophic to hyperplastic and eventually neoplastic involves the reactivation of basal stemness. The vacillating expression patterns of OM-SCMs confirm the role of keratins 5, 14, 19, CD44, β1-integrin, p63, sex-determining region Y box (SOX2), octamer-binding transcription factor 4 (Oct-4), c-MYC, B-cell-specific Moloney murine leukaemia virus integration site 1 (Bmi-1) and aldehyde dehydrogenase 1 (ALDH1) in OSF, OPMDs and OSCC. The downregulation of OM-SCMs in the atrophic epithelium of OSF and their upregulation during malignant transformation are illustrated with relevant literature in this review.

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Caspase-3 expression in normal oral epithelium, oral submucous fibrosis and oral squamous cell carcinoma

Cited by 20 publications

References 17 publications

Stress hormones promote DNA damage in human oral keratinocytes

Stress hormones promote DNA damage in human oral keratinocytes

Myrtenal averts apoptotic evasion of cancer cells in 7,12-dimethylbenz(a)anthracene induced experimental oral carcinogenesis

Loss of oral mucosal stem cell markers in oral submucous fibrosis and their reactivation in malignant transformation

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