###### Abstract  
Microalgae, eukaryotic unicellular plants that are distributed worldwide, have been shown to exert anti-proliferative and anticancer activities on various human cancer cell lines. An example of a microalgal bioactive compound is a chlorophyll breakdown product named Pheophorbide \(a\) (Ppu), which has been reported to have anti-proliferative properties against various cell lines. This compound has also been tested with light exposure in photodynamic therapy for cancer treatment. In this paper, we screened eleven marine microalgae against a panel of cancer cells, and evaluated the synergistic anti-proliferative effect with Pheophorbide \(a\), with and without photo-activation. The results showed significant anti-proliferative activity against melanoma cells when Ppu was combined with fraction E of the diatom _Cylindrotheca closterium_ plus 1 h photo-activation. Its activity was also analyzed using gene expression and Western blot experiments. Altogether, these data give new insights into the possible application of microalgae for photodynamic therapy. microalgae; _Cylindrotheca closterium_; Pheophorbide \(a\); photodynamic therapy; cancer; biotechnological applications +
Footnote †: journal: Medical  
immunomodulatory activities [13; 14; 15; 16; 17; 18; 19; 20; 21], and have also found applications in the aquaculture (such as for fish oil replacement in fish diets, as live prey diets or powder products), biodiesel and biomaterial sectors [22; 23; 24; 25; 26]. Considering that some microalgae (biomass or extracts) have received the \"GRAS\" (generally recognized as safe) status [27], there are now various microalgae-derived powder-based products on the market and recent investigations have also proposed them as ingredients in fresh pasta, cookies and yogurt [28; 29; 30]. In this study, various microalgal species (i.e., two _Chlamydomonas_ sp., _Dunaliella tertioleta_-Chlorophyta, _Asterionellosis glacialis_, _Cylindricalo discrerium_, _Ditylum brighttwellii_, _Trieres mobiliensis_, _Pseudo-nitzschia arenysensis_, _Pseudo-nitzschia fraudulenta_-Bacillusphorta, _Scrippsiella acuminata_-Miozoa, _Rhinomonas reticulata_-Cryptista) were tested on human cancer cell lines (i.e., melanoma, hepatocarcinoma and myeloma) and a non-cancerous cell line. The microalgae selected for this study included both diatoms, flagellates and one dinoflagellate, in order to screen different microalgal classes and increase the probability of finding activity. In addition, considering that different strains of the same genus may exert different bioactivities [10], we also selected two _Chlamydomonas_ (Chlorophyta) and two _Pseudo-nitzschia_ species (Bacillusphorta). Some of these microalgae were already tested in other studies for other possible applications. For example, [PERSON] et al. [31] showed that the diatom _Cylindricalo discrerium_ had anti-inflammatory activity and identified lysophosphatidylcholines and chlorophyll-derived molecules as active components. Total extracts of the diatom _Trieres mobiliensis_ (formerly _Odontella mobiliensis_) also showed anti-inflammatory activity on THP-1 (human acute monocytic leukemia cell line) with dose-dependent inhibition of tumor necrosis factor-\(\alpha\) production [10]. [PERSON] et al. [32] demonstrated a strong anti-proliferative activity of the flagellate _Dunaliella tertioleta_ (Chlorophyta) on the breast cancer cell line MCF-7 and the prostate cancer cell line LNCaPP. The natural xanthophyll pigment violaxanthin was identified as the bioactive component of the active \(D\). _tertioleta_ dichloromethane extracts [32]. Recently, [PERSON] and co-workers [16] tested another _Dunaliella tertioleta_ strain (CCMP 1320) on melanoma, hepatocellular liver carcinoma and two lung adenocarcinoma cell lines (A2058, HepG2, HCC827 and Calu-3, respectively) and isolated a glycerol 1-(9Z,12Z,15Z-octadecatrieneonate)-2-(4Z,7Z,10Z,13Z-hexadecetetraonate)-3-O-b-D-galactopyranoside as the active component with anti-proliferative activity against melanoma.