Development of Novel Photosensitizer Using the Buddleja officinalis Extract for Head and Neck Cancer

Abstract

Photodynamic therapy (PDT) is generally safer and less invasive than conventional strategies for head and neck cancer treatment. However, currently available photosensitizers have low selectivity for tumor cells, and the burden and side effects are so great that research is needed to develop safe photosensitizers. In this study, it was confirmed that the Buddleja officinalis (BO) extract, used in the treatment of inflammation and vascular diseases, shows fluorescence when activated by LED light, and, based on this, we aimed to develop a new photosensitive agent suitable for PDT. MTT, Diff-Quick® staining, and DCF-DA were performed to measure the effects of treating head and neck cancer cells with BO extract and 625 nm LED light (BO-PDT). Cell cycle, TUNEL, and western blot assays, as well as acridine orange staining, were performed to explore the mechanism of BO-PDT-induced cell death. We found that when the BO extract was irradiated with 625 nm LED light, it showed sufficient fluorescence and stronger intracellular toxicity and ROS effect than the currently commercially available hematoporphyrin. BO-PDT resulted in a decrease of mTOR activity that was correlated with an increase in the levels of ATG5, beclin-1, and LC3-II, which interfere with the formation of autophagosomes. In addition, BO-PDT induced the activation of PARP and led to an increase in the expression of proapoptotic protein Bax and a decrease in the expression of the antiapoptotic protein Bcl-2. Moreover, BO-PDT has been shown to induce the autophagy pathway 4 h after treatment, while apoptosis was induced 16 h after treatment. Finally, we confirmed that BO-PDT caused cell death of head and neck cancer cells via the intrinsic pathway. Therefore, we suggest that BO extract can be used as a new photosensitizer in PDT of head and neck cancer.

<p>Autophagy-Related Beclin 1 and Head and Neck Cancers</p>

“…119 Buddleja officinalis: Buddleja officinalis (BO) extract, which is a sensitizer to photodynamic therapy, may induce cell death of FaDu hypopharyngeal carcinoma cells. 120 The study showed that BO upregulated autophagy by increasing ATG5, Beclin 1, and LC3-II expression levels and decreased mTOR expression and promoted apoptosis by increasing Bax protein expression and decreasing Bcl-2 expression. This study also showed that crosstalk occurred between autophagy and apoptosis, and that activated autophagy occurred prior to activated apoptosis.…”

“…This study also showed that crosstalk occurred between autophagy and apoptosis, and that activated autophagy occurred prior to activated apoptosis. 120 …”

“…This study also showed that crosstalk occurred between autophagy and apoptosis, and that activated autophagy occurred prior to activated apoptosis. 120 Flavokawain B (FKB): Flavokawain B is a natural kava chalcone, which inhibits growth, migration, and invasion, and induces apoptosis of Tca thyroid cancer cells. During cytotoxicity of FKB, FKB induced autophagy by increasing LC3B-II and Beclin 1 expression and decreasing p62 expression.…”

Stoichioproteomics study of differentially expressed proteins and pathways in head and neck cancer

“…It is generally believed that the most illustrative risk factors are tobacco and alcohol, as well as poor oral hygiene, chronic mechanical irritation (Farsi et al, 2017) and HPV infection (Rodríguez Zorrilla et al, 2019). At present, the therapies of head and neck cancer involve surgery, radiotherapy (Karam and Raben, 2019), chemotherapy (Crooker et al, 2018), photodynamic therapy (Cho et al, 2018), and targeted therapy (Nisa et al, 2014). Despite these various therapies, patients always experience posttreatment side effects.…”

A Novel Fluorescent Dye Extracted from Buddleja officinalis for Labeling Mitochondria after Fixation

“…Few fluorescent products have previously been isolated from plants for cellular imaging [ 15 , 16 ]. In our previous studies, we reported that photosensitizers could be extracted from traditional plants and used for photodynamic treatment [ 17 , 18 ]. After treating with photosensitizers, fluorescence was identified around the nucleus where mitochondria are located.…”