<p>Silibinin restores the sensitivity of cisplatin and taxol in A2780-resistant cell and reduces drug-induced hepatotoxicity</p>

Abstract

Purpose Ovarian cancer is the most lethal cancer among all gynaecological malignancies. The combination theraputics of cisplatin and taxol is widely used in clinicals for ovarian cancer treatment. However, long-term use of cisplatin and taxol induces strong tolerance and hepatotoxicity. Since silibinin is a commonly used anti-hepatotoxic drug in Europe and Asia, the aim of this study was to determine whether silibinin could restore the sensitivity of combination use of cisplatin and taxol in drug-resistant human ovarian cancer cells and reduce drug-induced hepatotoxicity. Patients and methods Normal hepatocyte LO2 cells and A2780/DDP cells were treated with silibinin, cisplatin, taxol, cisplatin and taxol plus silibinin for 48 h. Cell viability was determined by MTT and long-term proliferation assay, while apoptosis and cell cycle progression were assessed by flow cytometric analysis. DNA damage was evluated by immunofluorescence assays. The metastatic activity of A2780/DDP was determined by cell adhesion assay. Results The addition of silibinin on cisplatin and/or toxal could sensitize the antitumor activity of cisplatin and toxal on A2780/DDP cells, supress cell-matrix adhesion of A2780/DDP, inhibit the cell proliferation, result in A2780/DDP cells apoptosis. In addition, silibinin could effectively reduce cisplatin and/or toxal-induced hepatotoxicity by protecting DNA from damage and restoring the potential of cell proliferation in cisplatin and/or toxal-treated LO2 cells. Conclusion Our results suggest that silibinin could restore the sensitivity of cisplatin and taxol in drug-resistant human ovarian cancer cells and reduce durg-induced hepatotoxicity in cell level.

Multidrug Resistance Modulation Activity of Silybin Derivatives and Their Anti-Inflammatory Potential

“…The observed higher activity of dehydrosilybin compared to silybin could be caused by the presence of the double bond on C-2,3 in ring B, which increases lipophilicity of dehydrosilybin, thus facilitating its interaction with the membrane proteins/lipids and enhancing the cytotoxic potential [50]. In agreement with our results, treatment of the ovarian carcinoma cell line (A2780/DPP) resistant to cisplatin and taxol with silybin also enhanced the sensitivity of the cells [22].…”

“…Silybin seems to be a prospective compound in this regard, as pre-incubation of P-gp-positive small-cell lung cancer (VPA17) cells at 30 µM for 5 days led to decreased IC 50 (concentration halving the viability) of etoposide [21]. Additionally, treatment of an ovarian carcinoma cell line (A2780/DPP) resistant to cisplatin and taxol with 50 µM silybin enhanced sensitivity of the cells to both drugs [22]. We have recently published modulation of P-gp expression by other flavonolignans, such as 2,3-dehydrosilychristin and anhydrosilychristin [23].…”

Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF

“…It has been widely used to treat and prevent many types of hepatobiliary disorders including alcoholic liver disease, nonalcoholic fatty liver disease, and mushroom poisoning 12 , 13 . Moreover, silibinin not only exert potent inhibitory effect on various types of cancer cells, such as breast cancer cells, prostate cancer cells, and glioma cells 7 , 14 , 15 , but also sensitizes glioma cells to TMZ, TRAIL or arsenic trioxide treatment and prevents hepatocyte injury induced by chemotherapy agent cisplatin 16 – 19 . Although silibinin could induce autophagic death in cancer cells 7 , 8 , the biochemical events downstream silibinin-induced autophagy remains unclear.…”

Silibinin Inhibit Cell Migration through Downregulation of RAC1 Gene Expression in Highly Metastatic Breast Cancer Cell Line

“…Silibinin is a polyphenolic flavonolignan of slymarin from seeds of milk thistle (Silybum marianum) and multitude published reports proved different anticancer efficacy of silibinin in experimental in vitro and in vivo models. These anticancer properties include apoptosis induction, inhibiting cell proliferation, angiogenesis, and inhibition of invasion in a variety of cancer models [12][13][14]. Silibinin has been revealed to be an effective chemotherapeutic and chemopreventive agent without unwanted side effects and therefore it could have potential clinical application for breast cancer treatment [15].…”