Abstract
Selenium has remained a controversial character in cancer research. While its antitumor effects have been widely demonstrated, further evidence is required to establish it as a robust treatment regime. Sodium selenite (SS), an inorganic selenium, reportedly affected the proliferation and redifferentiation of gastric cancer cells, but whether it could act as a complement to conventional chemotherapeutic drugs for combination therapy is uncertain. Herein, SGC-7901 and MGC-803 gastric cancer cells were treated with PADM (Ac-Phe-Lys-PABC-ADM), a prodrug of doxorubicin/adriamycin (ADM), and the combined antitumor effects of the two drugs were evaluated. Characterization after treatment revealed that although PADM exhibited antitumor effects individually by inhibiting the proliferation and migration of gastric cancer cells and inducing apoptosis, the addition of SS significantly amplified these effects. Furthermore, gastric cancer cell apoptosis triggered by the combined treatment of SS and PADM may involve the participation of mitochondrial apoptosis, as evidenced by the changes in mitochondrial morphology and occurrence of mitochondrial fission. Collectively, SS could be a strong complementary drug that accentuates the therapeutic potential of PADM in gastric cancer treatment and management, and its significance could contribute to unique and innovative anticancer strategies.
Highlights
With the rising incidence and high mortality of cancer, it has become the primary cause of death in China and emerged as a severe public health concern
In the PADM molecule, the specific substrate AcPhe-Lys is linked to ADM via PABC, which acts as a spacer
E related characteristics of cathepsin B have been applied in the development of new anticancer drugs based on molecular targeting [20]. e use of PADM takes advantage of the biological characteristics of local cathepsin B release in the process of gastric cancer invasion and metastasis [21], demonstrating that the toxicity of PADM was significantly reduced under exposure to low levels of cathepsin B
Summary
With the rising incidence and high mortality of cancer, it has become the primary cause of death in China and emerged as a severe public health concern. Its clinical application is limited because its toxic effects increase with increasing dose [6, 7]. To address this issue, an effective and low-toxicity chemotherapeutic prodrug has been developed in the form of the ADM precursor Ac-Phe-Lys-PABC-ADM (PADM) [8]. PADM is cleaved to release free ADM molecules, which exert their intended therapeutic impact [8]. In this way, the BioMed Research International toxicity of ADM is mitigated in healthy tissues, ensuring that the drug only targets cancer cells and is inactive otherwise
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