Synthesized Pheophorbide a‐mediated photodynamic therapy induced apoptosis and autophagy in human oral squamous carcinoma cells

Abstract

Background: Pheophorbide a (Pa) is a chlorine‐based photosensitizer derived from an ethnopharmacological herb, and our group recently synthesized Pa by the removal of a magnesium ion and a phytyl group from chlorophyll‐a. In this study, the effect of photodynamic therapy (PDT) with synthesized Pa was examined in a human oral squamous cell carcinoma (OSCC) cells. Methods: Cells were treated with PDT with Pa, and reactive oxygen species (ROS) and mitochondrial membrane potential [ΔΨ (m)] were examined. Apoptosis was measured using annexin V staining and immunoblot. Autophagy was characterized by the increase in LC3B‐II and the formation of autophagosome and acidic vesicular organelles (AVOs). Results: Pa‐PDT inhibited the proliferation of OSCC cells in a dose‐dependent manner. Pa‐PDT increased the number of apoptotic cells by inactivating ERK pathway. Pa‐PDT also induced autophagy in OSCC cells evidenced by the increased levels of LC3 type II expression and the accumulation of AVOs. The inhibition of autophagy enhanced Pa‐PDT‐mediated cytotoxicity through an increase in necrosis. Conclusions: These results suggest that synthesized Pa‐PDT exerts anti‐tumor effects by inducing apoptosis and autophagy and provide novel evidence that Pa‐PDT induces autophagy, and autophagy inhibition enhances Pa‐PDT‐mediated necrosis in OSCC cells.

Photodynamic therapy with the novel photosensitizer chlorophyllin f induces apoptosis and autophagy in human bladder cancer cells

“…Recently, accumulating evidence indicated that ROS, the direct cytotoxic agents of PDT, can also stimulate autophagy with functional consequences varying from cytoprotection to the activation of autophagic cell death . This finding is consistent with the conclusions of the research groups of Kessel D and Ahn MY; they also found PDT could induce autophagy in cancer cells . Furthermore, in this study, we found chlorophyllin f would distribute in the lysosomes of 5637 and T24 cells, which also indicated that f‐PDT might induce autophagy in the two cell lines.…”

HOXC6 regulates the antitumor effects of pheophorbide a-based photodynamic therapy in multidrug-resistant oral cancer cells

“…Recently, we synthesized pheophorbide a (Pa) by removing a magnesium ion and a phytyl group from chlorophyll-a. Our studies reported that Pa-based PDT can effectively inhibit tumor cell proliferation in several cancer cells, including skin and head and neck cancer (16)(17)(18). Other research groups reported that Pa-based PDT can effectively inhibit tumor cell proliferation in hepatocellular carcinoma (19,20), colon cancer (21), pigmented melanoma (22) and breast adenocarcinoma (23); however, its therapeutic potential in oral cancer (especially instances of MDR) has not been fully investigated.…”

Hyperbaric Oxygen Combined with 5-Aminolevulinic Acid Photodynamic Therapy Inhibited Human Squamous Cell Proliferation

“…24) PDT involves the interaction of photosensitizers, light and oxygen. 25) PDT was reported to inhibit cancers through different cell death pathways. 26) In this study, ALA-PDT significantly suppressed A431 cell proliferation via inducing mitochondria-dependent intrinsic pathway cell apoptosis, which was evidenced with up-regulation of active caspase 3, Bax, active caspase 9 and Afaf1 levels, and down-regulation of Bcl-2.…”

“…This result was consistent with study from Mee et al, who reported that Pa (a kind of Photosensitizer)-PDT exerted anti-tumor effects by inducing apoptosis and autophagy, and autophagy inhibition enhances Pa-PDT-mediated apoptosis in human oral squamous carcinoma cells. 25)…”