Synthesis of three cisplatin-conjugated asymmetric porphyrin photosensitizers for photodynamic therapy.

Photodynamic therapy provides a promising solution for treating various cancer types. In this study, three distinct asymmetric porphyrin-cisplatin complex photosensitizers (ZnPt-P1, ZnPt-P2, and ZnPt-P3) were synthesized, each having unique side chains. Through a set of experiments involving singlet oxygen detection and density functional theory, ZnPt-P1 was demonstrated to have excellent efficacy, exceeding that of ZnPt-P2 and ZnPt-P3. Notably, ZnPt-1 showed significant phototoxicity while maintaining low dark toxicity when tested on HepG2 cells. Additionally, further examination revealed that ZnPt-P1 had the capability to generate reactive oxygen species within cancer cells when exposed to light irradiation. Taken together, these results highlight the potential of ZnPt-P1 as a photosensitizer for use in photodynamic therapy. This study contributes to enhancing cancer treatment methodologies and provides insights for the future development of innovative drugs for photosensitization.

Saturated free fatty acid sodium palmitate-induced lipoapoptosis by targeting glycogen synthase kinase-3ß activation in human liver cells.

BACKGROUND: Elevated serum saturated fatty acid levels and hepatocyte lipoapoptosis are features of nonalcoholic fatty liver disease (NAFLD). AIM: The purpose of this study was to investigate saturated fatty acid induction of lipoapoptosis in human liver cells and the underlying mechanisms. METHODS: Human liver L02 and HepG2 cells were treated with sodium palmitate, a saturated fatty acid, for up to 48 h with or without lithium chloride, a glycogen synthase kinase-3ß (GSK-3ß) inhibitor, or GSK-3ß shRNA transfection. Transmission electron microscopy was used to detect morphological changes, flow cytometry was used to detect apoptosis, a colorimetric assay was used to detect caspase-3 activity, and western blot analysis was used to detect protein expression. RESULTS: The data showed that sodium palmitate was able to induce lipoapoptosis in L02 and HepG2 cells. Western blot analysis showed that sodium palmitate activated GSK-3ß protein, which was indicated by dephosphorylation of GSK-3ß at Ser-9. However, inhibition of GSK-3ß activity with lithium chloride treatment or knockdown of GSK-3ß expression with shRNA suppressed sodium palmitate-induced lipoapoptosis in L02 and HepG2 cells. On a molecular level, inhibition of GSK-3ß expression or activity suppressed sodium palmitate-induced c-Jun-N-terminal kinase (JNK) phosphorylation and Bax upregulation, whereas GSK-3ß inhibition did not affect endoplasmic reticulum stress-induced activation of unfolded protein response. CONCLUSIONS: The present data demonstrated that saturated fatty acid sodium palmitate-induced lipoapoptosis in human liver L02 and HepG2 cells was regulated by GSK-3ß activation, which led to JNK activation and Bax upregulation. This finding indicates that GSK-3ß inhibition may be a potential therapeutic target to control NAFLD.

[Therapeutic effect and prognosis of interferon therapy after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma associated with hepatitis B virus].

OBJECTIVE: To evaluate the therapeutic effect of interferon therapy after transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma associated with hepatitis B virus. METHODS: Sixty-two patients with advanced primary hepatocellular carcinoma associated with hepatitis B virus was randomly divided into 2 groups. Thirty-one cases were treated with TACE and Interferon. Thirty-one cases with TACE only. HBV DNA, clinical effect, intrahepatic tumor recurrence rate and survival rate were studied. RESULTS: Of the 31 patients in TACE+IFN group, 17 (54.8%) were negative for HBV DNA at the end of treatment. None of TACE group was negative for HBV DNA. The intrahepatic tumor recurrence rate at 1 year and 2 years in TACE+IFN group was 16.1%, 29.0%, compared with 38.7%, 61.3% in TACE group (chi-square = 3.97, chi-square 6.51, P < 0.05). The survival rate in the former was 83.9% and 74.2% respectively, compared with that of 61.3% and 38.7% in the latter (chi-square = 3.97, chi-square = 7.94, P < 0.05). CONCLUSION: Interferon therapy after transcatheter arterial chemoembolization resulted low recurrence and long survival in patients with hepatocellular carcinoma associated with hepatitis B virus. This method showed fewer side effects and should be recommended.