Berberine as a photosensitizing agent for antitumoral photodynamic therapy: Insights into its association to low density lipoproteins

Abstract

Recent years have seen a growing interest in Berberine, a phytochemical with multispectrum therapeutic activities, as anti-tumoral agent for photodynamic therapy (PDT). In this context, low density lipoproteins (LDL) play a key role in the delivery of the photosensitizer in tumor cells. We correlate the physicochemical parameters of the berberine association to LDL with the influence of LDL-delivery on its accumulation in a glioma cell line and on its photo-induced activity in view of antitumor PDT. Our results evidence an important binding of 400 berberine molecules per LDL. Changes in berberine and apoprotein fluorescence suggest different fixation types, involving various LDL compartments including the vicinity of the apoprotein. The berberine association to LDL does not affect their recognition by the specific B/E receptors, of which over-expression increases the cellular uptake of LDL-preloaded berberine. Fluorescence microscopy evidences the mitochondrial labeling of the glioma model cells, with no significant modification upon LDL-delivery. Moreover, the cellular delivery of berberine by LDL increases its photocytotoxic effects on such cells. So, this research illustrates the potential of berberine as a photosensitizing agent for PDT, in particular due to their behavior towards LDL as plasma vehicles, and gives insights into its mechanisms of cell uptake.

Biologically active isoquinoline alkaloids covering 2014–2018

“…174 The PI3K-Akt and mitogen-activated protein kinase (MAPK) signaling pathways in the treatment of thyroid carcinoma also were affected. 175,176 A related isoquinoline alkaloid, coptisine (165), also affected PI3K/Akt and mitochondrial-associated apoptotic pathways, 177 and exhibited remarkable cytotoxic activities against HCT-116 cells by activating the caspase protease family, inducing G1-phase cell cycle arrest and increasing apoptosis. 178 The protoberberine alkaloid palmatine (166) induced cell apoptosis in MCF-7 breast cancer cells; after the treatment (1 μM, 10.8 J/cm 2 ), the early apoptotic and late apoptotic rates increased significantly up to 21.16% and 9.86% in photodynamic therapy.…”

Berberine nanoparticles for promising sonodynamic therapy of a HeLa xenograft tumour

“…16 Though it is reported that berberine can release ROS by photodynamic therapy, our research showed that both BBR cavitation and ROS can be driven by sonodynamic therapy in vivo. 17,18 All the information we gained in this study indicates that BBRNPs-SDT might present a promising and better noninvasive tumor therapy approach for both preclinical and clinical cancer studies.…”

Role of Photoactive Phytocompounds in Photodynamic Therapy of Cancer

“…Furthermore, alkaloids induce the formation of intracellular ROS in cancer cells, which leads to the destruction of cancer cell metabolism [ 140 , 141 , 142 , 143 ]. The photochemically best-known alkaloid is berberine; Luiza Andreazza et al [ 146 ], Bhattacharyya et al [ 147 ] and Inbaraj et al [ 81 ] reported the antitumour activity of berberine upon UV and blue light irradiation. The irradiation of berberine at 410 nm proved to be effective in controlling brain cancer cell growth [ 146 ].…”

“…The photochemically best-known alkaloid is berberine; Luiza Andreazza et al [ 146 ], Bhattacharyya et al [ 147 ] and Inbaraj et al [ 81 ] reported the antitumour activity of berberine upon UV and blue light irradiation. The irradiation of berberine at 410 nm proved to be effective in controlling brain cancer cell growth [ 146 ]. Beta-carboline and harmine are also a noticeable alkaloid with a photoactive nature and are reported to produce a significant amount of ROS after irradiation [ 148 ], which is considered an important feature of potent PSs.…”