Photodynamic Therapy Enhanced the Antitumor Effects of Berberine on HeLa Cells

Abstract

In this study we investigated the antineoplastic effects of Berberine (BBR)-mediated photodynamic therapy (PDT) on HeLa cells and its related mechanisms. The CCK-8 assay and flow cytometry were used to evaluate the proliferation and apoptosis of cells respectively. In addition, changes in protein expression levels were assessed using western blot. BBR at dose of 10 mg/kg was injected intraperitoneally to mice with tumors and PDT treatments were performed 24 hours later. In vivo imaging systems were used to evaluate the fluorescence of BBR. In vitro, PDT significantly enhanced the effects of BBR on inducing cell apoptosis and inhibiting proliferation. The in vivo results showed that the fluorescence intensity in the PDT group was decreased compared with that in the BBR group. Tumor weights and tumor size in the PDT group were less than those in the control group; however, when BBR was applied without PDT, no significant differences were observed between the BBR and control group. The results of western blot showed that PDT enhanced the inhibitory effects of BBR on the mammalian target of rapamycin (mTOR) signaling pathway, that may partly explain the potential underlying mechanisms.

Research progress of berberine mediated photodynamic therapy (Review)

“…Warowicka et al ( 59 ) investigated the potential anticancer effects of a protoberberine alkaloidal fraction on HeLa and C33A cervical cancer cells. Liu et al ( 15 ) verified the antitumor effects of BBR-PDT in xenograft animal models, and revealed the role of the PI3K/AKT/mTOR signaling pathway.…”

“…BBR is sensitive to light and can react in the presence of changing energy levels, such as several other secondary metabolites, including coralyne, sauguinarine and palmatine ( 15 , 17 ). All plant compounds have specific biological functions, whose effects have been demonstrated to be effective in animal cells, including humans ( 17 – 23 ).…”

“…4 . Among these, the mechanisms of BBR-PDT in treating tumors may involve inhibiting cell proliferation, inducing apoptosis and autophagy, and altering the expression of proteins or genes ( 15 ). However, there are a few studies currently investigating these mechanisms.…”

“…Wang et al ( 14 ) studied the photodynamic activity of BBR on cancer cells in 1986. Our recent studies demonstrated that BBR-mediated PDT and sonodynamic therapy (SDT) significantly inhibit tumor cells in vivo ( 15 , 16 ). As a photosensitizer, BBR possesses several advantages, such as easy production, low cost and various pharmacological effects, including antitumor functions ( 15 ).…”

“…Our recent studies demonstrated that BBR-mediated PDT and sonodynamic therapy (SDT) significantly inhibit tumor cells in vivo ( 15 , 16 ). As a photosensitizer, BBR possesses several advantages, such as easy production, low cost and various pharmacological effects, including antitumor functions ( 15 ). However, BBR also possesses several disadvantages, including toxicity and poor water solubility ( 16 ).…”