## 6 Curcumin in Oral Cancer  
The most common form of oral cancer making up 90% of oral malignancy cases is oral squamous cell carcinoma (OSCC) [173]. The disease occurs more frequently in men than women and is usually unnoticed at early stages which may contribute to its high mortality rates [174]. The clinical manifestations include an ulcer with fissuring, raised exophytic margins, lumps or lesions. As the most important risk factors that may eventually lead to OSCC development, alcohol and tobacco use, some viral agents and premalignant conditions are mentioned. It was found that curcumin, as a compound revealing the ability to affect the signaling pathways in the cell, can act as an apoptosis-inducing agent preventing the proliferation of cancer cells. Moreover, the compound can also be considered an adjunct therapeutic agent, supporting conventional anticancer therapy, preventing drug resistance and supporting radiotherapy. It was shown that curcumin can interact with reactive oxygen species and signaling molecules including nuclear factor kappa B (NF-kB) contributing to the induced cell death. Moreover, it can play an important role in cell cycle arrest [175]. Some novel studies suggest that curcumin can be also used as photosensitizer in photodynamic therapy of cancer [176]. The active ingredient is delivered to the cells usually in nanoencapsulated form to improve the uptake efficacy. Curcumin present in the cells upon the irradiation produces reactive oxygen species triggering a sequence of mechanisms leading eventually to cell death. Considering the fact that this effect is activated only as a result of irradiation, the phototoxic effect can be limited to tumor only, without affecting the healthy tissues. The literature reports show some promising results regarding cancer cell lines [176; 177; 178]. However, photodynamic therapy involving curcumin as photosensitizer is more frequently investigated as an antimicrobial approach, targeting bacterial [179] and fungal cells [180]. There are several available literature reports focusing on the application of curcumin as an active agent towards OSCC cells in vitro. [PERSON] et al. [181] investigated curcumin as a potential photosensitizer in photodynamic therapy of OSCC. It was shown that the compound was effective towards cancer cells even at low concentration. However, further studies investigating animal models are necessary. Moreover, some beneficial effects of curcumin without irradiation have also been reported. Curcumin affected the mechanisms responsible for cancer progression and metastasis, decreasing the invasiveness [182], and also stimulated the immune response towards tongue OSCC which was reported by [PERSON] et al. [183]. It is noteworthy that the compound was effective both in in vitro experiments and in vivo studies performed with the use of animal models with oral cancer induced with 4-nitroquinoline-1-oxide. Figure 6 depicts the treatment scheme along with the results recorded for the curcumin-treated group of animals and the control group which was given DMSO instead. \begin{table}
\begin{tabular}{c c c c c} \hline
**Condition** & **Dosage Form** & & **The Most Important Findings** & **Reference** \\ \hline Gingivitis & gel & \(\bullet\) & both curcumin- and chlororeidine-based treatments were effective & \\  & & & \(\bullet\) & chlororeidine performed better in terms of anti-plaque and anti-inflammatory properties & [161] \\  & & & \(\bullet\) & no statistically significant difference between curcumin- and chlororeidine-based treatments & [162] \\  & mouthwash & & \(\bullet\) & the same antimicrobial activity & \\ \hline \end{tabular}
\end{table} 
Table 2: _Cont._Curcumin was also investigated as a potential adjuvant therapeutic for co-administration with standard anticancer therapy. [PERSON] et al. [184] investigated the effects of commonly applied anticancer drugs, i.e., docetaxel, doxorubicin, 5-fluorouracil and cisplatin, combined with curcumin against head and neck squamous cell carcinoma cell line (NT8e).