Expression of Sex Hormones in Oral Squamous Cell Carcinoma: A Systematic Review on Immunohistochemical Studies

Saranya, R; Chandini, R; Mohideen, Khadijah; Adtani, Pooja N; Subramani, Vijayanirmala; Balasubramaniam, Murali

doi:10.7759/cureus.25384

Cited by 4 publications

(3 citation statements)

References 27 publications

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“…For the clinical application, the production rate of Compounds A and B per month (at present, 50~60 mg each) should be scaled up. The present study suggests that Compounds A and B may destroy oral cancer cells that express estrogen receptors [ 37 , 38 ] without affecting normal cells in the oral cavity and the nervous system. Potential inhibition of estrogen-related receptor signaling pathways opens up possibilities for further research and application of these compounds in the field of hormone-dependent cancer and other diseases.…”

Section: Discussionmentioning

confidence: 86%

A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs

et al. 2023

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Background. Many anti-cancer drugs used in clinical practice cause adverse events such as oral mucositis, neurotoxicity, and extravascular leakage. We have reported that two 3-styrylchromone derivatives, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (Compound A) and 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one (Compound B), showed the highest tumor-specificity against human oral squamous cell carcinoma (OSCC) cell lines among 291 related compounds. After confirming their superiority by comparing their tumor specificity with newly synthesized 65 derivatives, we investigated the neurotoxicity of these compounds in comparison with four popular anti-cancer drugs. Methods: Tumor-specificity (TSM, TSE, TSN) was evaluated as the ratio of mean CC50 for human normal oral mesenchymal (gingival fibroblast, pulp cell), oral epithelial cells (gingival epithelial progenitor), and neuronal cells (PC-12, SH-SY5Y, LY-PPB6, differentiated PC-12) to OSCC cells (Ca9-22, HSC-2), respectively. Results: Compounds A and B showed one order of magnitude higher TSM than newly synthesized derivatives, confirming its prominent tumor-specificity. Docetaxel showed one order of magnitude higher TSM, but two orders of magnitude lower TSE than Compounds A and B. Compounds A and B showed higher TSM, TSE, and TSN values than doxorubicin, 5-FU, and cisplatin, damaging OSCC cells at concentrations that do not affect the viability of normal epithelial and neuronal cells. QSAR prediction based on the Tox21 database suggested that Compounds A and B may inhibit the signaling pathway of estrogen-related receptors.

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Section: Discussionmentioning

confidence: 86%

A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs

et al. 2023

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“…To further confirm such an association among the estrobolome and cancer, some studies have found that the estrobolome has a different composition in people with or without oral cancer; in fact, people with oral cancer showed a higher presence of estrobolome bacteria (Saranya et al 2022).…”

Section: Discussionmentioning

confidence: 99%

“…In fact, tumors associated with high estrogen levels are characterized by marked hormonal signaling through the estrogens receptor (ER) interactions; as such, these pathways drive unreasonably high cellular proliferation. This increased cell growth coincides with enhanced mutation rates, due to metabolic activation facilitated by cytochrome P450 enzymes, ultimately leading to both genotoxic damage and the induction of aneuploidy (Saranya et al 2022).…”

Section: Introductionmentioning

confidence: 99%

Oral–Gut–Estrobolome Axis May Exert a Selective Impact on Oral Cancer

Tatullo,

Nor,

Orrù

et al. 2024

J Dent Res

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A subset of bacterial species that holds genes encoding for β-glucuronidase and β-galactosidase, enzymes involved in the metabolism of conjugated estrogens, is called the “estrobolome.” There is an emerging interest embracing this concept, as it may exert a selective impact on a number of pathologies, including oral cancer. Although the estrobolome bacteria are typically part of the gut microbiota, recent experimental pieces of evidence have suggested a crosstalk among oral and gut microbiota. In fact, several oral bacterial species are well represented also in the gut microbiota, and these microbes can effectively induce the estrobolome activation. The main pathways used for activating the estrobolome are based on the induction of the expression patterns for 2 bacterial enzymes: β-glucuronidase and aromatase, both involved in the increase of estrogen released in the bloodstream and consequently in the salivary compartment. Mechanistically, high estrogen availability in saliva is responsible for an increase in oral cancer risk for different reasons: briefly, 1) estrogens directly exert biological and metabolic effects on oral mucosa cells; 2) they can modulate the pathological profile of some bacteria, somewhere associated with neoplastic processes (i.e., Fusobacterium spp., Parvimonas ssp.); and 3) some oral bacteria are able to convert estrogens into carcinogenic metabolites, such as 4-hydroxyestrone and 16α-hydroxyestrone (16α-OHE), and can also promote local and systemic inflammation. Nowadays, only a small number of scientific studies have taken into consideration the potential correlations among oral dysbiosis, alterations of the gut estrobolome, and some hormone-dependent cancers: this lack of attention on such a promising topic could be a bias affecting the full understanding of the pathogenesis of several estrogen-related oral pathologies. In our article, we have speculated on the activity of an oral–gut–estrobolome axis, capable of synergizing these 2 important microbiotas, shedding light on a pilot hypothesis requiring further research.

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Sex steroid hormones: an overlooked yet fundamental factor in oral homeostasis in humans

Cornejo Ulloa,

Krom,

Schoonmade

et al. 2024

Front. Endocrinol.

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Sex steroid hormones (SSH) are extremely versatile molecules with a myriad of physiological functions. Next to their well-known role in sexual development and reproduction, SSH play active roles in practically every tissue in the human body, including the oral cavity. It has long been demonstrated that periodontal tissues express SSH receptors and therefore are responsive to the presence of SSH. Interestingly, SSH not only interact with the periodontal tissues but also with other tissues in the oral cavity such as dental enamel, pulp, cementum, oral mucosa, and salivary glands. Questions concerning the possible physiological functions of these receptors and their role in maintenance of oral health, remain unanswered. The purpose of this scoping review was to gather and summarize all the available evidence on the role of SSH in physiological processes in the oral cavity in humans. Two comprehensive literature searches were performed. References were screened and selected based on title, abstract and full text according to our inclusion criteria. Both searches yielded 18,992 results of which 73 were included. Results were divided into four categories: (1) Periodontium; (2) Dental structure; (3) Mucosa; and (4) Salivary glands. The interaction of these tissues with progestagens, androgens and estrogens are summarized. Sex steroid hormones are an overlooked yet fundamental factor in oral homeostasis. They play important roles in the development and function of the periodontium, dental structure, mucosa and salivary glands. Dentists and healthcare providers should consider these hormonal factors when assessing and treating oral health conditions.

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Expression of Sex Hormones in Oral Squamous Cell Carcinoma: A Systematic Review on Immunohistochemical Studies

Cited by 4 publications

References 27 publications

A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs

A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs

Oral–Gut–Estrobolome Axis May Exert a Selective Impact on Oral Cancer

Sex steroid hormones: an overlooked yet fundamental factor in oral homeostasis in humans

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