Background:
Astaxanthin (AST) shows a large range of beneficial effects together with anti-cancer
and antioxidation properties. Human Serum Albumin (HSA) is the most abundant protein in blood plasma which
plays the role of a depot and transport protein for many exogenous compounds. However, whether HSA could
enhance AST-induced cytotoxic effects in human ovarian cancer cells has not been examined to date.
Objective:
This study aims to explore the anticancer effect and the molecular mechanism of AST combine with
HSA induced cytotoxicity in ovarian cancer SKOV3 cells.
Methods:
The ovarian cancer SKOV3 cells were treated by AST combined with HSA to study the effects of cell
proliferation, cell morphology, cell cycle arrest, related protein expression, nuclear transfer, cell migration, and
drug-resistant.
Results:
Our data confirmed that AST+HSA treatment enhanced the anticancer effects of AST, arrested G1
phase cell cycle and induced apoptosis in SKOV3 cells. AST+HSA induced apoptosis via mitochondrial apoptotic
pathways was related to the increased ratio of Bcl-2/Bax and activation of caspase-3. Besides, exposure of
cells to AST+HSA triggered the inactivation of NF-κB and activation p53 and MAPKs signaling pathways.
Furthermore, AST+HSA significantly overcome the drug-resistant and inhibited the migration of SKOV3 cells.
Conclusion:
AST combined treatment with HSA considerably inhibited NF-κB expression and translocation to
nucleus, thereby improving the AST-induced cytotoxic effect on SKOV3 cells. These findings may provide
rationale to combine AST with HSA for the treatment of ovarian cancer.
Aim: To investigate the relationship between PI3K/Akt/NF-κB cellular signal pathway and the expression of P-gp and LRP in multidrug resistance (MDR) cell of nasopharyngeal carcinoma.
Method: The PI3K, p-Akt and NF-κB/p65 as the activity of PI3K/Akt/NF-κB were detected by Western blot. The expressions of LRP and P-gp were detected by Western blot and real-time PCR.
Result: The RIs of CNE/DDP group to DDP, 5-Fu, VCR, ADR and PTX were 35.04, 18.14, 24.13, 12.00 and 10.18, respectively. The RIs of LY-294002 group were 11.77, 5.83, 3.07, 3.86 and 3.34, and PDTC group were 11.08, 6.55, 7.66, 2.18 and 4.05. The expressions of PI3K, p-Akt and NF-κBp65, LRP and P-gp were increased and mRNA of LRP and P-gp were up-regulated in CNE/DDP. The expression of p-Akt in LY-294002 group was down-regulated. The expression of NF-κB p65 in PDTC group was decreased. The mRNA of LRP and P-gp in LY-294002 group and PDTC group were decreased.
Conclusion: MDR of nasopharyngeal carcinoma cell can be regulated by activating PI3K/Akt/NF-κB signal pathway and then increase the expression of P-gp and LRP. The MDR of nasopharyngeal carcinoma cell can be reversed by inhibiting PI3K/Akt/NF-κB signal pathway.
Two new compounds, named (Z)-7,4'-dimethoxy-6-hydroxyaurone-4-O-β-glucopyranoside (1) and ()-4-O-(4-O-β-D-glucopyranosylcaffeoyl)quinic acid (2), were isolated from the endophytic fungus Penicillium citrinum of Avicennia marina. Their structures were elucidated on the basis of spectroscopic analysis. Additionally, compound 2 exhibited potent chemoreversal activity, mainly by inhibiting P-glycoprotein efflux pump function.
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