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Sclareol, a labdane diterpene phytochemical in the various genus Salvia of the herbaceous plant has been anti-carcinogenic properties on numerous human cancer cell lines. Till known the anticancer properties of sclareol on human oral KB cancer cells are not revealed. Therefore, we scrutinized the viability, nucleate damage associated with apoptosis in KB cells treated with sclareol.The cytotoxicity of KB cells displayed to sclareol was evaluated by hexosaminidase and trypan blue exclusion assay. Apoptosis was noticed by Hoechst staining and affirmed by nucleate damage. We discovered that sclareol treatment for KB cells with expressively lessened cell proliferation or viability and evoked cell death in a dose-dependent manner compared with untreated control. Sclareol stimulated inhibition of growing of oral KB cells came along to be induction nucleate damage. Our data proved that sclareol on stimulated apoptosis in human oral KB cancer cells through nucleate damage. These observations recommend the anti-cancer properties of sclareol.

Sclareol has demonstrated a broad variety of biological activities that belong to the antioxidant anti-inflammatory and anticancer activities that are used in traditional medicine. In the current study, we intended to explore the antitumor possible of sclareol along 7, 12-dimethylbenz (a) anthracene (DMBA) evoked golden Syrian hamster’s buccal pouch carcinogenesis. Lipid peroxidation and antioxidants were assessed by the buccal tissue, and plasma of DMBA evoked golden Syrian hamster buccal pouch carcinogenesis of observational animals. We observed 100% of tumor establishment and noted defects in the biochemical restrictions of lipid peroxidation and antioxidants and also histopathological observations of carcinogenesis in the hamster’s buccal pouch in DMBA only. Sclareol (20 mg/b.wt) has significantly inhibited the tumor burden, tumor volume, and increased phase II detoxification enzymes, antioxidant level, lipid peroxidation, and also phase I enzymes and has improved the histopathologically changes during carcinogenesis in the buccal pouch of DMBA induced golden Syrian hamster. The outcomes of the present scrutinized study proposed that aiming biochemically and histopathologically that act upon the inheritance of cancer characteristics is an effectual system for chemoprevention. Therefore, our results resolved that sclareol has probably owing to its antioxidant or scavenging properties of free radical and transition act on phase I and II enzymes in regards to the evacuation of metabolites carcinogenesis, which is evoked by DMBA in hamster’s buccal pouch.

Oral cancer is a major cause of morbidity and mortality in developing countries. Despite advances in chemotherapy for the cancer management, the survival rate has not yet been improved. Dietary nutrient has been receiving a lot of attention and interest in the chemotherapeutic development. [6]-Shogaol is a major bioactive compound identified in ginger that possesses many pharmacological properties. The aim of the present study is to investigate the effect of [6]-shogaol on 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch (HBP) carcinogenesis. Oral squamous cell carcinoma induced in HBP by painting with 0.5% 7,12-dimethylbenz(a)anthracene (DMBA), thrice in a week for 16 weeks. We observed 100% tumour incidence, decreased levels of lipid peroxidation, antioxidant, and phase II detoxification enzymes (GST, GR and GSH) in DMBA-induced hamsters. Further, enhanced activity of phase I enzymes (cytochrome p450 and b5) and over-expression of mutant p53, Bcl-2 and decreased expression of wild type p53 and Bax were noticed in DMBA-induced hamsters. Our results indicated that [6]-shogaol (10, 20 and 40 mg/kg body weight) treated with DMBA-painted hamsters, considerably reversed tumour incidence, improved antioxidant status, phase II detoxification enzymes, and also inhibit lipid peroxidation and phase I enzymes. Moreover, [6]-shogaol inhibits mutant p53 and Bcl-2 expression and significantly restored normal p53, Bax levels. Thus, we concluded that [6]-shogaol prevents DMBA-induced HBP carcinogenesis through its antioxidant as well as modulating apoptotic signals.

The Notch signaling pathway is an evolutionarily conserved cell signaling pathway. It plays a central role in cell fate decisions and differentiation. The bioavailability of sclareol has been widely studied due to its anti-carcinogenic and antioxidant effects. However, chemo preventive effects of sclareol on notch signaling in 7, 12-dimethylbenz [a] anthracene (DMBA) induced hamster buccal pouch(HBP) carcinogenesis remain to be fully elucidated. In the present study, tumors were induced by applying 0.5% DMBA topically to HBP thrice a week for 14 weeks and sclareol was orally administered at a dose of 20mg/kg body weight on alternate days of DMBA painting. We analyzed expression of Notch signaling in DMBA induced oral squamous cell carcinoma (OSCC) in experimental oral carcinogenesis and inhibition of notch signaling by sclareol. This study thus observed up regulation of Notch1, Notch2, Jagged1, Hes1 and Hey1 in DMBA alone induced hamsters. Furthermore, oral administration of sclareol led to reduced Notch1, Notch2 activation and expression of Jagged-1 and its downstream targets of Hes-1 and Hey-1 in tumor bearing hamsters. In addition, sclareol treatment increased pro-apoptotic and decreased anti-apoptotic proteins survival indicating apoptosis through activation of caspase 3, and promoting cell death by dysregulation of cyclin D1 levels in tumor bearing hamsters. Immunohistochemical examination showed that Notch intracellular domain accumulates in the nucleus of cells in DMBA induced hamster buccal pouch carcinogenesis, and Jagged1 was found to be dysregulated in sclareol treated tumor animals. In conclusion, the results provide an important new insight of Notch signaling pathway for a potential therapeutic target for oral cancer. Citation Format: Aiyavu Chinnaiyan, Anandhi Nallu, Suresh Kathiresan. Sclareol induces apoptosis and inhibits notch signaling in hamster oral carcinogenesis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 10.

Worldwide, oral squamous cell carcinoma (OSCC) is the sixth most common cancer & ranked as second most common cancer in India. The most implicated etiologic factors in the development of oral cancer is the use of tobacco, alcohol & also HPV infection. Aescin, a pentacyclic triterpenoid saponin mixtures derived from Aesculus hippocastanum L (horse chestnut) that has been used as traditional herbal medicine, exists the pharmacodynamic properties, anti- edematous, anti-inflammatory & antitumor. The present study, Tumors were induced by applying 0.5% DMBA topically to hamster buccal pouch (HBP) thrice a week for 14 weeks & Aescin was orally administered at a various dose of 40 mg/kg body weight on alternate days of DMBA painting. We observed, reduced the tumor incidence, diminished lipid peroxidation, & elevation of antioxidants, liver marker enzymes by Aescin. Furthermore, aescin induced apoptosis in DMBA induced tumor bearing animals significantly inhibited cell to cell communication of Notch-1, Notch-2 & its ligand & Jagged-1 leads to inhibited expression of the Notch downstream signaling target Hes-1 & Hey-1 analyzed by immunohistochemical analysis. These results clearly suggest that Aescin prevents lipid peroxidation, protects the antioxidant defense system, prohibit the dysplasia & anti-carcinogenic potential. we concluded; the results provide an important new insight of Notch signaling pathway & aescin might be developed as a potential chemo preventive agent for oral cancer. Key words: Oral cancer, aescin, antioxidant, apoptosis, chemopreventive, Notch signaling Citation Format: Hemavardhini Ramadoss, Suresh Kathiresan, Sanjay Gupta. Apoptosis & anti-proliferative nature of Aescin on 7,12 dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinogenesis via downregulating Notch signaling [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 129.

The incidence of Head and Neck cancer in increasing worldwide. The major risk factor for these cancers includes viral infection, smoking, alcohol and tobacco consumption. Natural agents have often exhibited medicinal properties with usefulness in treating various human ailments including cancer. Aescin is one of the most prominent constituent of Aesculus hippocastanum L. (Hippocastanaceae) seeds has been conventionally used as medicinal herb. We determined the anticancer effect of aescin on human oral carcinoma (KB) cells and human laryngeal carcinoma (HEp-2) cells. Treatment of KB cells with 25µM and HEp-2 cells with 22µM aescin for 24 hours suppressed proliferation in these cells and induced morphological changes consistent with apoptosis. Exposure of both cell lines to aescin resulted in marked increase in reactive oxygen species, loss of cell viability, and reduction of cellular glutathione levels resulting in depolarization of mitochondrial membrane potential thereby increasing oxidative DNA damage in KB and HEp-2 cells. Furthermore, aescin-mediated apoptosis in these cells progress via notch signaling as shown by downregulation of Notch1, Notch2, Jagged-1, HES1, and HEY1 expression. Taken together, our results demonstrate that aescin initiate apoptosis in KB and HEp-2 cells by increasing oxidative damage implying that aescin might be developed as a potential chemotherapeutic agent for the treatment of human oral and laryngeal cancer. Key word: Oral carcinoma, Aescin, apoptosis, anti-proliferative, Notch signaling Citation Format: Suresh Kathiresan, Hemavardhini Ramadoss, Sanjay Gupta. Aescin, a triterpene saponin induces apoptosis & oxidative damage in human oral & laryngeal cancer cells via notch signaling [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6557.

Gramine, a natural indole alkaloid found in Hordeum vulgare has been possesses anti-mutagenic properties. The aim of the present study was to evaluate the effect of gramine on inflammation and proliferation in 7,12-dimethylbenz[a]anthracene(DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Epidermal growth factor receptor (EGFR) tyrosine kinase phosphorylation trigged PI3K/Akt/mTOR and JAK signaling that activates NF-κB and STAT3. In contrast, gramine suppressed EGFR tyrosine kinase phosphorylation and simultaneously inhibiting PI3K/Akt/mTOR and JAK phosphorylation, thereby blockage NF-κB and STAT3 nuclear translocation. Attenuation of these oncogenic signals leads to downregulated iNOS, COX-2, TNF-α, IL-6, cyclin D1 and PCNA protein expressions. In addition, gramine enhanced the expression of the tumor suppressors p53, p21(WAF1/CIP1) and Gsk-3β by inhibiting MDM2. These results suggested that gramine exhibited anti-inflammation and anti-proliferation effects via suppressed EGFR/PI3K/Akt/mTOR/ IKK/NF-κB and JAK/STAT3 signaling pathways.

Background The search for naturally occurring agents in routinely consumed foods that may inhibit cancer development is of high priority. [6]-Paradol is a pungent phenolic bioactive component from ginger with well- documented health promoting antioxidant, antimutagenic, antigenotoxic and anti-inflammatory properties. However, anticarcinogenic effects have yet to be fully explored. The objectives of the present study were therefore to assess protective effects against 7,12-dimethylbenz(a)anthracene (DMBA) induced buccal pouch carcinogenesis in male golden Syrian hamsters. Methods Oral squamous cell carcinomas developed in the left buccal pouch of hamsters on painting with 0.5% of DMBA, three times in a week. To assess the apoptotic associated gene expressing potential of [6]-paradol, it was orally administered to DMBA treated hamsters on alternate days from DMBA painting for 14 weeks. Results We observed 100% tumor formation with marked levels of neoplastic changes and altered the expression of apoptotic associated gene (p53, bcl-2, caspase-3 and TNF-α) was observed in the DMBA alone painted hamsters as compared to control hamsters. Oral administration of [6]-paradol at a dose of 30 mg/kg b.wt to DMBA treated animals on alternative days for 14 weeks significantly reduced the neoplastic changes and improved the status of apoptosis associated gene expression. Conclusion These observations confirmed that [6]-paradol acts as a tumor suppressing agent against DMBA induced oral carcinogenesis. We also conclude that [6]-paradol also effectively enhances apoptosis- associated gene expression in DMBA treated animals.