The effect of aloe emodin–encapsulated nanoliposome‐mediated r‐caspase‐3 gene transfection and photodynamic therapy on human gastric cancer cells

Abstract

Gastric carcinoma (GC) has high incidence and mortality rates in China. Surgery and chemotherapy are the main treatments. Photodynamic therapy (PDT) has become a new treatment modality, appearing in recent experimental studies and clinical trials in various tumors. This study explores the combined effect of gene transfection with PDT on GC cells using aloe emodin (AE)–encapsulated nanoliposomes, which acted as gene carrier as well as one photosensitizer (PS). AE‐encapsulated nanoliposomes (nano‐AE) were prepared by reverse evaporation method. Electron microscopy and nano‐ZS90 analyzer were used to detect its morphology, size, and wavelength. Western blot was used to detect the expression of the caspase‐3 after transfection. MTT assay and flow cytometry were employed to determine the cytotoxic and apoptotic rates, respectively. Hoechst 33342 staining was adopted to detect the morphological changes in death gastric cancer cells. Cellular reactive oxygen species (ROS) contents were measured by DCFH‐DA staining. Outcomes demonstrated that the nano‐AE has good properties as gene delivery carriers as well as a PS. The group in which the recombinant plasmid of r‐caspase‐3 was transfected had higher protein expression of the caspase‐3 than controls, meanwhile the proliferation rates of the transfected cells were inhibited by the nano‐AE‐mediated PDT in an energy‐dependent manner. In addition, in the transfected cells, the death rate increased to 77.3% as assessed 12 h after PDT (6.4 J/cm2). Hochest 33342 staining also revealed that the death rate increased significantly in the transfected group compared with other groups. Compared to control groups, the production of ROS in nano‐AE PDT group had quadrupled in SGC‐7901 cells as early as 1 h after PDT, while it is similar to the group of nano‐AE transfection and PDT. Nano‐AE‐mediated r‐caspase‐3 gene transfection coupled with PDT could inhibit the proliferation rate and increase the apoptotic rate remarkably in human gastric cancer cells.

Mitochondrial pathway and endoplasmic reticulum stress participate in the photosensitizing effectiveness of AE‐PDT in MG63 cells

“… have demonstrated that the cytoskeletal alteration was potentially involved in anoikis induced by AE‐PDT in human lung carcinoma H460 cells. Our previous study also demonstrated that AE‐PDT produced significant photocytotoxicity and induced apoptosis in tumors . However, the molecular mechanism of AE‐PDT is still not completely clear.…”

Aloe‐emodin: A review of its pharmacology, toxicity, and pharmacokinetics

“…Additionally, aloe‐emodin was used as a photosensitizer to explore the effect of photodynamic therapy (PDT) in human gastric cancer SGC‐7901 cells. Li et al () explored the combined effect of gene transfection with PDT on SGC‐7901 cells using aloe‐emodin‐encapsulated nanoliposomes. The results revealed that aloe‐emodin‐encapsulated nanoliposomes‐mediated r‐caspase‐3 gene transfection coupled with PDT remarkably inhibited the proliferation of SGC‐7901 cells.…”

“…The results revealed that aloe‐emodin‐encapsulated nanoliposomes‐mediated r‐caspase‐3 gene transfection coupled with PDT remarkably inhibited the proliferation of SGC‐7901 cells. The main mechanisms were attributed to aloe‐emodin‐induced apoptosis and necrosis of gastric cancer cells (Li et al, ). Similarly, Lin et al () also showed that aloe‐emodin‐induced PDT exerted an inhibitory effect on SGC‐7901 cells in dose‐dependent and energy‐dependent manners.…”

“…Aloe‐emodin (1,8‐dihydroxy‐3‐hydroxymethyl‐anthraquinone; Figure 1) is a natural anthraquinone derivative that occurs in many widely used Chinese medicinal herbs, such as Cassia occidentalis , Rheum palmatum L., Aloe vera , and Polygonum multiflorum Thunb, that are used as traditional medicines in many countries (Panigrahi, Mudiam, Vashishtha, Raisuddin, & Das, ; Huang, Lu, Shen, Chuang, & Ong, ; Hamman, ; Yi, Leung, Lu, Zhang, & Chan, ). Currently, aloe‐emodin has attracted much attention for its remarkable antineoplastic activity on different tumor cells, such as lung, gastric, hepatic, melanoma, breast, and colon cancer cells (Huang et al, ; Lee, Lin, Yang, Leung, & Chang, ; Li et al, ; Lu, Shen, Chung, & Ong, ; Lu, Shen, Ong, & Chung, ; Suboj, Babykutty, Srinivas, & Gopala, ; Tabolacci et al, ). Furthermore, aloe‐emodin has been demonstrated to exhibit a wide spectrum of pharmacological effects, such as antivirus, anti‐inflammatory, antibacterial, antiparasitic, neuroprotective, and hepatoprotective (Divya, Panonnummal, Gupta, Jayakumar, & Sabitha, ; Hu, Zhang, Meng, Wang, & Wang, ; Li et al, ; Tao et al, ; Wang, Chung, Ho, Wu, & Chang, ; Woo et al, ).…”

Drug Delivery Systems of Natural Products in Oncology

“…Li et al investigated the effect of transfection of r-caspase-3 with nanoliposomes loaded with AE and photodynamic therapy in human gastric cancer cells [ 165 ]. Nano-AE was employed as delivery carrier for plasmid r-caspase-3 transfection, which, consequently, induced apoptosis, and also as photosensitizer for photodynamic therapy.…”