Human Oral Carcinoma Cells Research Articles

Synergistic Action of Vanillic Acid-Coated Titanium Oxide Nanoparticles: Targeting Biofilm Formation Receptors of Dental Pathogens and Modulating Apoptosis Genes for Enhanced Oral Anticancer Activity.

The prevalence of bacterial and fungal infections is caused by S. aureus, S. mutans, E. faecalis, and Candida albicans are often associated with dental illnesses. In the present study, a unique strategy was used to combat these diseases by fabricating titanium dioxide nanoparticles (TiO2 NPs) conjugated with the plant-based molecule vanillic acid (VA). To confirm the structural characterization of the synthesized VA-TiO2 NPs, an extensive analysis was carried out utilizing methods such as SEM, FTIR, and XRD. Assessments for scavenging reactive oxygen species were performed to evaluate its antioxidant capability. Furthermore, a zone of inhibition test targeting pathogenic oral bacteria was used to assess the antibacterial efficacy of VA-TiO2 NPs. Molecular modeling investigations were performed to better understand the interactions among vanillic acid and dental pathogen receptors using the Autodock program. The findings indicated that VA-TiO2 NPs exhibited strong free radical scavenging activity. Additionally, they showed excellent antibacterial action towards dental pathogens, with a minimum inhibition level of 60 μg/mL. Furthermore, at doses of 15 μg/mL, 30 μg/mL, 60 μg/mL, and 120 μg/mL, VA-TiO2 NPs demonstrated concentration-dependent apoptotic impacts on human oral carcinoma cells. Apoptotic gene over-expression was identified by the molecular perspectives that revealed the anticancer mechanism of VA-TiO2 NPs on KB cells. This study highlights the promising suitability of VA-TiO2 NPs for dental applications due to their robust antioxidant, anticancer, and antimicrobial characteristics. These nanoparticles present an evident prospect for addressing oral pathogen challenges and improving overall oral health.

Novel alloxazine analogues: design, synthesis, and antitumour efficacy enhanced by kinase screening, molecular docking, and ADME studies

This study describes the development of novel alloxazine analogues as potent antitumor agents with enhanced selectivity for tumour cells. Twenty-nine out of 45 newly compounds were investigated in vitro for their growth inhibitory activities, against two human tumour cell lines, namely, the human T-cell acute lymphoblastoid leukaemia cell line (CCRF-HSB-2) and human oral epidermoid carcinoma cell line (KB), and the antitumor agent “Ara-C” was used as a positive reference in this investigation. Compounds 9e and 10J were the highest among their analogues, against both tumour cell lines (CCRF-HSB-2 and KB). Correlation analyses demonstrated a strong relationship between the IC50 values and AutoDock binding free energy or calculated inhibition (Ki ). The study delves into structure–activity relationships (SARs) through advanced modelling tools integrated with structure-based drug design (SBDD) using GOLD 5.2.2, AutoDock 4.2, and Accelrys Discovery Studio 3.5. Physicochemical properties, pharmacokinetics, drug-likeness, and toxicity predictions of the most potent alloxazine derivatives were conducted using ProTox-II and Swiss ADME for effective antitumor agents with improved selectivity.

Usnic acid alleviates inflammatory responses and induces apoptotic signaling through inhibiting NF-ĸB expressions in human oral carcinoma cells.

Usnic acid (UA) is a unique bioactive substance in lichen with potential anticancer properties. Recently, we have reported that UA can reduce 7,12-dimethylbenz[a] anthracene-induced oral carcinogenesis by inhibiting oxidative stress, inflammation, and cell proliferation in a male golden Syrian hamster in vivo model. The present study aims to explore the relevant mechanism of cell death induced by UA on human oral carcinoma (KB) cell line in an in vitro model. We found that UA can induce apoptosis (cell death) in KB cells by decreasing cell viability, increasing the production of reactive oxygen species (ROS), depolarizing mitochondrial membrane potential (MMP) levels, causing nuclear fragmentation, altering apoptotic morphology, and causing excessive DNA damage. Additionally, UA inhibits the expression of Bcl-2, a protein that promotes cell survival, while increasing the expression of p53, Bax, Cytochrome-c, Caspase-9, and 3 proteins in KB cells. UA also inhibits the expression of nuclear factor-κB (NF-κB), a protein that mediates the activation of pro-inflammatory cytokines such as TNF-α and IL-6, in KB cells. Furthermore, UA promotes apoptosis by enhancing the mitochondrial-mediated apoptotic mechanism through oxidative stress, depletion of cellular antioxidants, and an inflammatory response. Ultimately, the findings of this study suggest that UA may have potential as an anticancer therapeutic agent for oral cancer treatments.

F127/chlorin e6-nanomicelles to enhance Ce6 solubility and PDT-efficacy mitigating lung metastasis in melanoma.

Photodynamic Therapy (PDT) is a promising paradigm for treating cancer, especially superficial cancers, including skin and oral cancers. However, the effectiveness of PDT is hindered by the hydrophobicity of photosensitizers. Here, chlorin e6 (Ce6), a hydrophobic photosensitizer, was loaded into pluronic F127 micelles to enhance solubility and improve tumor-specific targeting efficiency. The resulting Ce6@F127 Ms demonstrated a significant increase in solubility and singlet oxygen generation (SOG) efficiency in aqueous media compared to free Ce6. The confocal imaging and fluorescence-activated cell sorting (FACS) analysis confirmed the enhanced internalization rate of Ce6@F127 Ms in murine melanoma cell lines (B16F10) and human oral carcinoma cell lines (FaDu). Upon laser irradiation (666nm), the cellular phototoxicity of Ce6@F127 Ms against B16F10 and FaDu was approximately three times higher than the free Ce6 treatment. The in vivo therapeutic investigations conducted on a murine model of skin cancer demonstrated the ability of Ce6@F127 Ms, when combined with laser treatment, to penetrate solid tumors effectively, which resulted in a significant reduction in tumor volume compared to free Ce6. Further, the Ce6@F127 Ms demonstrated upregulation of TUNEL-positive cells, downregulation of proliferation markers in tumor tissues, and prevention of lung metastasis with insignificant levels of proliferating cells and collagenase, as validated through immunohistochemistry. Subsequent analysis of serum and blood components affirmed the safety and efficacy of Ce6@F127 Ms in mice. Consequently, the developed Ce6@F127 Ms exhibits significant potential for concurrently treating solid tumors and preventing metastasis. The photodynamic formulation holds great clinical translation potential for treating superficial tumors.

Design, synthesis and anticancer activity studies of 3-(coumarin-3-yl)-acrolein derivatives: Evidenced by integrating network pharmacology and vitro assay.

Coumarin derivatives have diverse structures and show various significant biological activities. Aiming to develop more potent coumarin derivatives for cancer treatment, a series of coumarin acrolein hybrids were designed and synthesized by using molecular hybridization approach, and investigated for their antiproliferative activity against A549, KB, Hela and MCF-7 cancer cells as well as HUVEC and LO2 human normal cells. The results indicated that most of the synthesized compounds displayed remarkable inhibitory activity towards cancer cells but low cytotoxicity on normal cells. Among all the compounds, 5d and 6e were the most promising compounds against different cancer cell lines, especially for A549 and KB cells. The preliminary action mechanism studies suggested that compound 6e, the representative compound, was capable of dose-dependently suppressing migration, invasion and inducing significant apoptosis. Furthermore, the combined results of network pharmacology and validation experiments revealed that compound 6e induced mitochondria dependent apoptosis via the PI3K/AKT-mediated Bcl-2 signaling pathway. In summary, our study indicated compound 6e could inhibit cell proliferation, migration, invasion and promote cell apoptosis through inhibition of PI3K/AKT signaling pathway in human oral epidermoid carcinoma cells. These findings demonstrated the potential of 3-(coumarin-3-yl)-acrolein derivatives as novel anticancer chemotherapeutic candidates, providing ideas for further development of drugs for clinical use.

Molecular Modeling and In Vitro Evaluation of Piplartine Analogs against Oral Squamous Cell Carcinoma.

Cancer is a principal cause of death in the world, and providing a better quality of life and reducing mortality through effective pharmacological treatment remains a challenge. Among malignant tumor types, squamous cell carcinoma-esophageal cancer (EC) is usually located in the mouth, with approximately 90% located mainly on the tongue and floor of the mouth. Piplartine is an alkamide found in certain species of the genus Piper and presents many pharmacological properties including antitumor activity. In the present study, the cytotoxic potential of a collection of piplartine analogs against human oral SCC9 carcinoma cells was evaluated. The analogs were prepared via Fischer esterification reactions, alkyl and aryl halide esterification, and a coupling reaction with PyBOP using the natural compound 3,4,5-trimethoxybenzoic acid as a starting material. The products were structurally characterized using 1H and 13C nuclear magnetic resonance, infrared spectroscopy, and high-resolution mass spectrometry for the unpublished compounds. The compound 4-methoxy-benzyl 3,4,5-trimethoxybenzoate (9) presented an IC50 of 46.21 µM, high selectively (SI > 16), and caused apoptosis in SCC9 cancer cells. The molecular modeling study suggested a multi-target mechanism of action for the antitumor activity of compound 9 with CRM1 as the main target receptor.

Structural alterations in cell organelles induced by photodynamic treatment with chlorin p6 -histamine conjugate in human oral carcinoma cells probed by 3D fluorescence microscopy.

We have explored the intracellular cell organelle's structural alterations after photodynamic treatment with chlorin p6 -histamine conjugate (Cp6 -his) in human oral cancer cells. Herein, the cells were treated with Cp6 -his (10μm) and counterstained with organelle-specific fluorescence probes to find the site of intracellular localization using confocal microscopy. For photodynamic therapy (PDT), the cells were exposed to ~30 kJ/m2 red light (660 ± 20 nm) to induce ~90% cytotoxicity. We used the three-dimensional (3D) image reconstruction approach to analyze the photodynamic damage to cell organelles. The result showed that Cp6 -his localized mainly in the endoplasmic reticulum (ER) and lysosomes but not in mitochondria and Golgi apparatus (GA). The 3D model revealed that in necrotic cells, PDT led to extensive fragmentation of ER and fragmentation and swelling of GA as well. Results suggest that the indirect damage to GA occurred due to loss of connection between ER and GA. Moreover, in damaged cells with no sign of necrosis, the perinuclear ER appeared condensed and surrounded by several small clumps at the peripheral region of the cell, and the GA was observed to form a single condensed structure. Since these structural changes were associated with apoptotic cell death, it is suggested that the necrotic and apoptotic death induced by PDT with Cp6 -his is determined by the severity of damage to ER and indirect damage to GA. The results suggest that the indirect damage to cell organelle apart from the sites of photosensitizer localization and the severity of damage at the organelle level contribute significantly to the mode of cell death in PDT.

BMP4 Regulates EMT to be Involved in non-Syndromic Cleft lip With or Without Palate.

In the previous study, we identified bone morphogenetic protein 4 (BMP4) responsible for non-syndromic cleft lip with or without cleft palate (NSCL/P). We aimed to elucidate the effects and mechanisms of BMP4 on epithelial-mesenchymal transition (EMT) through Smad1 signaling pathway to be involved in NSCL/P. The human oral epidermoid carcinoma cells (KBs) were transfected with plasmids or small interfering RNA (siRNA) to build the models. The migration of the cells was evaluated by transwell assay. Western blotting and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the expressions of BMP4, E-cadherin, N-cadherin, EMT-related transcription factors snal1 and snal2, matrix metalloproteinase 2 (MMP2), MMP9, Smad1, and phosphorylated Smad1. In the overexpression group, the migration number of cells was increased significantly. The protein expression of E-cadherin was decreased significantly, while the protein expression level of the N-cadherin was increased significantly. The protein and mRNA expressions of MMP2, MMP9, snal1, and snal2 were significantly higher. The expression level of Smad1 was not significantly changed, while the phosphorylation of Smad1 was significantly increased. In the BMP4-siRNA group, the migrating number cells was significantly decreased. The protein expression of E-cadherin was increased significantly, while the expression of N-cadherin was significantly decreased. The protein and mRNA expressions of MMP2, MMP9, snal1, and snal2 were significantly lower than that of the control group. The expressions of Smad1 and phosphorylation of Smad1 were not significantly changed. BMP4 enhances cell migration and promotes cell EMT through Smad1 signaling pathway. Abnormal BMP4 mediates migration and EMT through other relevant signaling pathways resulting in NSCL/P. The study provides new insight into the mechanisms of NSCL/P associated with BMP4.n.

Real-Time Monitoring the Cytotoxic Effect of Andrographolide on Human Oral Epidermoid Carcinoma Cells.

Andrographolide is an active diterpenoid compound extracted from Andrographis paniculata. It exhibits antiinflammatory and anticancer effects. Previous studies show that it is non-toxic to experimental animals. The leading causes of cancer are chronic inflammation and high blood glucose. This study determines the cytotoxic effect of andrographolide on cellular morphology, viability, and migration for human oral epidermoid carcinoma cell Meng-1 (OEC-M1). We use electric cell-substrate impedance sensing (ECIS) to measure the subsequent overall impedance changes of the cell monolayer in response to different concentrations of andrographolide for 24 h (10–100 µM). The results for exposure of OEC-M1 cells to andrographolide (10–100 µM) for 24 h show a concentration-dependent decrease in the overall measured resistance at 4 kHz. AlamarBlue cell viability assay and annexin V also show the apoptotic effect of andrographolide on OEC-M1 cells. A reduction in wound-healing recovery rate is observed for cells treated with 30 μM andrographolide. This study demonstrates that ECIS can be used for the in vitro screening of anticancer drugs. ECIS detects the cytotoxic effect of drugs earlier than traditional biochemical assays, and it is more sensitive and shows more detail.

MiR-10a-5p inhibits the migration and invasion of human oral carcinoma cells by targeting PIK3CA through PI3K/AKT/mTOR pathway

miR-10a-5p inhibits the migration and invasion of human oral carcinoma cells by targeting PIK3CA through PI3K/AKT/mTOR pathway

Stromal Barrier-Dismantled Nanodrill-Like and Cancer Cell-Targeted pH-Responsive Polymeric Micelles for Further Enhancing the Anticancer Efficacy of Doxorubicin.

Cancer-associated fibroblasts (CAFs) were believed to establish a tight physical barrier and a dense scaffold for tumor cells to make them maintain immunosuppression and drug resistance, strongly hindering nanoparticles to penetrate into the core of tumor tissues and limiting the performance of tumor cell-targeted nanoparticles. Here, we fabricated the substrate Z-Gly-Pro of fibroblast activation protein α (FAPα) and folic acid-codecorated pH-responsive polymeric micelles (dual ligand-modified PEOz-PLA polymeric micelles, DL-PP-PMs) that possessed nanodrill and tumor cell-targeted functions based on Z-Gly-pro-conjugated poly(2-ethyl-2-oxazoline)-poly(D,l-lactide) (ZGP-PEOz-PLA), folic acid (FA)-conjugated PEOz-PLA (FA-PEOz-PLA), and PEOz-PLA for cancer therapy. The micelles with about 40 nm particle size and a narrow distribution exhibited favorable pH-activated endo/lysosome escape induced by their pH responsibility. In addition, the enhancement of in vitro cellular uptake and cytotoxicity to folate receptors or FAPα-positive cells for doxorubicin (DOX)/DL-PP-PMs compared with DOX/PP-PMs evidenced the dual target ability of DOX/DL-PP-PMs, which was further supported by in vivo biodistribution results. As expected, in the human oral epidermal carcinoma (KB) cells xenograft nude mice model, the remarkable enhancement of antitumor efficacy for DOX/DL-PP-PMs with low toxicity was observed compared with DOX/FA-PP-PMs and DOX/ZGP-PP-PMs. The possible mechanism was elucidated to be the dismantling of the stromal barrier by nanodrill-like DOX/DL-PP-PMs via the deletion of CAFs evidenced by the downregulation of α-SMA and inhibition of their functions proved by the decrease in the microvascular density labeled with CD31 and the reduction in the extracellular matrix detected by the collagen content, thereby promoting tumor penetration and enhancing their uptake by tumor cells. The present research offered an alternative approach integrating anticancer and antifibrosis effects in one delivery system to enhance the delivery efficiency and therapeutic efficacy of anticancer drugs.

Cytotoxic and antibacterial depsidones from the endophytic fungus Chaetomium brasiliense isolated from Thai rice

Four new depsidones, mollicellins V-Y (1-4), together with eight known depsidones (5-12) were isolated from the endophytic fungus, Chaetomium brasiliense, detached from stems of Thai rice. Their structures were determined by extensive spectroscopic methods. Mollicellins X, H, and F (3, 8 and 10) showed potent cytotoxicity against the human oral epidermoid carcinoma (KB) cell line, and mollicellin F (10) also showed a potent cytotoxicity against the human hepatocellular carcinoma (HepG2) cell line. Besides, mollicellin B (11) exhibited cytotoxicity against the colorectal adenocarcinoma (HT-29) cell line. Moreover, most of the isolated depsidones displayed potent antibacterial activity against Gram-positive bacteria, Bacillus cereus and Bacillus subtilis, and several of them showed moderate activity against Methicillin-resistant Staphylococcus aureus (MRSA) and clinical isolates of S. aureus. In addition, a few of them also showed moderate activity against a Gram-negative bacteria Pseudomonas aeruginosa.

UNUSUALLY LIPID PRODUCTION BY THE MARINE-DERIVED FUNGI Penicillium restrictum

Using marine-derived fungi as a source of lipid production holds promise as an alternative to industrial lipid production for health and nutrition in the future. In the present study, this strain showed a high production of lipid, about plus 80% of the total lipids in the host-derived medium. Gas chromatography analysis of fungal lipids revealed the presence of saturated (mainly palmitic acid C16: 0 and stearic acid C18: 0) and unsaturated fatty acid (mainly linoleic acid C18: 2, oleic acid C18: 1). These findings suggest this marine-derived fungus is a promising source for lipid production in various industrial applications. In particular, a fraction containing glycolipids of the crude extract exhibited potential cytotoxic activity on human oral epidermal carcinoma cell lines. This result is very interesting to further isolate and determine the molecular structure of bioactive glycolipids.

In Vitro Evaluation of Anticancer Activity (Efficacy) of a Novel Ayurvedic Polyherbal Formulation on Human Oral Carcinoma Cell Line SCC-40.

In Vitro Evaluation of Anticancer Activity (Efficacy) of a Novel Ayurvedic Polyherbal Formulation on Human Oral Carcinoma Cell Line SCC-40.

Pathways Related to the Anti-Cancer Effects of Metabolites Derived from Cerrado Biome Native Plants: An Update and Bioinformatics Analysis on Oral Squamous Cell Carcinoma.

Oral cancer is a significant health problem worldwide. Oral squamous cell carcinoma (OSCC) is a malignant neoplasm of epithelial cells that mostly affects different anatomical sites in the head and neck and derives from the squamous epithelium or displays similar morphological characteristics. Generally, OSCC is often the end stage of several changes in the stratified squamous epithelium, which begin as epithelial dysplasia and progress by breaking the basement membrane and invading adjacent tissues. Several plant-based drugs with potent anti-cancer effects are considered inexpensive treatments with limited side effects for cancer and other diseases. The aim of this review is to explore whether some Brazilian plant extracts or constituents exhibit anti-tumorigenic activity or have a cytotoxic effect on human oral carcinoma cells. Briefly, OSCC and several metabolites derived from Brazilian plants (i.e., flavonoids, vinblastine, irinotecan, etoposide and paclitaxel) were used as keywords to search the literature on PubMed, GenBank and GeneCards. The results showed that these five chemical compounds found in Cerrado Biome plants exhibit anti-neoplastic effects. Evaluating the compounds revealed that they play a main role in the regulation of cell proliferation. Preserving and utilising the biodiversity of our planet, especially in unique ecosystems, such as the Cerrado Biome, may prove essential to preserving and promoting human health in modern contexts.

Exosome-Based Molecular Transfer Activity of Macrophage-Like Cells Involves Viability of Oral Carcinoma Cells: Size Exclusion Chromatography and Concentration Filter Method.

Extracellular vesicles (EV) heterogeneity is a crucial issue in biology and medicine. In addition, tumor-associated macrophages are key components in cancer microenvironment and immunology. We developed a combination method of size exclusion chromatography and concentration filters (SEC-CF) and aimed to characterize different EV types by their size, cargo types, and functions. A human monocytic leukemia cell line THP-1 was differentiated to CD14-positive macrophage-like cells by stimulation with PMA (phorbol 12-myristate 13-acetate) but not M1 or M2 types. Using the SEC-CF method, the following five EV types were fractionated from the culture supernatant of macrophage-like cells: (i) rare large EVs (500–3000 nm) reminiscent of apoptosomes, (ii) EVs (100–500 nm) reminiscent of microvesicles (or microparticles), (iii) EVs (80–300 nm) containing CD9-positive large exosomes (EXO-L), (iv) EVs (20–200 nm) containing unidentified vesicles/particles, and (v) EVs (10–70 nm) containing CD63/HSP90-positive small exosomes (EXO-S) and particles. For a molecular transfer assay, we developed a THP-1-based stable cell line producing a GFP-fused palmitoylation signal (palmGFP) associated with the membrane. The THP1/palmGFP cells were differentiated into macrophages producing palmGFP-contained EVs. The macrophage/palmGFP-secreted EXO-S and EXO-L efficiently transferred the palmGFP to receiver human oral carcinoma cells (HSC-3/palmTomato), as compared to other EV types. In addition, the macrophage-secreted EXO-S and EXO-L significantly reduced the cell viability (ATP content) in oral carcinoma cells. Taken together, the SEC-CF method is useful for the purification of large and small exosomes with higher molecular transfer activities, enabling efficient molecular delivery to target cells.

Anticancer potential of sclareol against human KB oral carcinoma cell line invitro

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.

Effects of salinomycin on proliferation and apoptosis of oral squamous cell carcinoma

To investigate the effects of salinomycin on the proliferation and apoptosis of oral squamous carcinoma cells and to further understand the mechanisms of these effects. The human oral squamous carcinoma cell line CAL-27 was cultured in different concentrations of salinomycin and cisplatin. After co-culture with 0, 1, 2, 4, 8, 16 and 32 μmol/L salinomycin or 0, 1.25, 2.5, 5, 10, 20, 40 and 80 μmol/L cisplatin for 24 hours and 48 hours, the proliferation of oral squamous carcinoma cells were detected by cell counting kit-8(CCK-8) assay. After being exposed to 0, 2, 4, 8 μmol/L salinomycin and 0, 5, 10, 20 μmol/L cisplatin for 48 hours, the cell cycle of oral squamous carcinoma cells was detected by flow cytometry assay, and Western blot analysis was performed to analyze the expressions of cysteine-containing aspartate-specific proteases-3(Caspase-3), cysteine-containing aspartate-specific proteases-9(Caspase-9), poly ADP-ribose polymerase (PARP), protein kinase B (Akt) and phosphorylated protein kinase B (p-Akt) protein in oral squamous carcinoma cells. Both salinomycin and cisplatin significantly inhibited the proliferation of oral squamous cell carcinoma CAL-27 cells in a time- and dose-dependent manner. However, compared with the first-line chemotherapeutic drug cisplatin, salinomycin showed stronger anti-proliferation activity in oral squamous carcinoma cells than cisp-latin (P < 0.001). After being exposed to 8 μmol/L salinomycin, CAL-27 cells exhibited markedly higher proportion in quiescent/ first gap phases (40.40%±1.99% vs. 64.46%±0.90%, P < 0.05), and had a significantly lower proportion in synthesis phases and second gap / mitosis phases (24.32%±2.30% vs. 18.73%±0.61%, P < 0.05; 35.01%±1.24% vs. 16.54%±1.31%, P < 0.05) compared with the dimethyl sulfoxide control group; moreover cisplatin didn't show cell-cycle specific effect on CAL-27. Western blot proved that salinomycin could up-regulate the expressions of Caspase-3 and Caspase-9 protein in oral squamous cell carcinoma CAL-27 cells (P < 0.05). At the same time, the levels of PARP, Akt and p-Akt protein were down-regulated (P < 0.05). Compared with cisplatin, salinomycin has a better inhibitory effect on the proliferation of oral squamous carcinoma cells and blocks the cell cycle process at the quiescent / first gap phase. At the same time, salinomycin could trigger apoptosis of oral squamous carcinoma cells and the mechanism is associated with the Akt/p-Akt signaling pathway.

Abstract 6557: Aescin, a triterpene saponin induces apoptosis &amp; oxidative damage in human oral &amp; laryngeal cancer cells via notch signaling

Abstract 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 &amp; oxidative damage in human oral &amp; 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.

Domino [4 + 2] Annulation Access to Quinone-Indolizine Hybrids: Anticancer N-Fused Polycycles.

A highly efficient synthetic route to new quinone-indolizine hybrids was accomplished from quinones and N-substituted pyrrole-2-carboxaldehydes via a domino Michael addition-aldol condensation-aromatization sequence through which the central pyridine ring was constructed in atom-economical and environment-friendly manner. Post modification of the resulting products was also demonstrated, enabling further expansion of this heterocyclic chemical space. Biological evaluation of the quinone-indolizine hybrids revealed potent anticancer effects in human prostate adenocarcinoma cells (PC-3) and oral adenosquamous carcinoma cells (CAL-27).