Polysaccharopeptide enhances the anticancer activity of doxorubicin and etoposide on human breast cancer cells ZR-75-30

Abstract

In search of natural bioactive microbial compounds with adjuvant properties, we have previously showed that the polysaccharopeptide (PSP), isolated from Chinese medicinal mushroom Coriolus versicolor, was able to enhance the cytotoxicity of certain S-phase targeted-drugs on human leukemic HL-60 cells via some cell-cycle and apoptotic-dependent pathways. The present study aimed to investigate whether the synergism of mechanisms of PSP with certain chemotherapeutic drugs also applies to human breast cancer. PSP treatment enhanced the cytotoxicity of doxorubicin (Doxo), etoposide (VP-16) but not cytarabine (Ara-C). Bivariate bromodeoxyuridine (BrdUrd)/DNA flow cytometry analysis estimated a longer DNA synthesis time (Ts) for the PSP treated cancerous cells suggesting that PSP enhanced the apoptotic effect of Doxo and VP-16 via creating an S-phase trap in the human breast cancer cell line ZR-75-30. The participation of PSP in the apoptotic machinery of the chemotherapeutic agents was further supported by a reduced ratio of protein expression of Bcl-x L /Bax of the cancer cells. This study provides further insight into the synergistic mechanisms of PSP and supports the hypothesis that the anti-cancer potentials of PSP is not limited to leukemia but may also be used as an adjuvant therapy for breast cancers.

The cell cycle effects of docosahexaenoic acid on human metastatic hepatocellular carcinoma proliferation

“…The cell cycle kinetics analysis was achieved by using the bivariate BrdUrd/DNA flow cytometry technique as previously described by our group (24) and other investigators (25)(26)(27). The method is based on simultaneous measurement of the total incorporation or the rate of incorporation of the thymidine analog, BrdUrd, into newly synthesized DNA.…”

“…Staining of cells for bivariate analysis of BrdUrd/ DNA flow cytometry analysis was performed as previously described by our group (24). Prior to staining of 2x10 6 BrdUrd incorporated cells, fixative was removed by washing twice with PBS and the DNA of cells were partially denatured by incubation with 2 M HCl for 20 min at room temperature.…”

“…The bivariate BrdUrd/DNA analysis allows separation of cells according to the cell-cycle phase (24,25). By repeating the bivariate BrdUrd/DNA analysis of labeled cells at different time points, it is possible to determine the rate of progression of BrdUrd-labeled cells as they accumulate more DNA.…”

“…The movement of the BrdUrdlabeled cells (cycling cells) between the G 0 /G 1 and G 2 /M cell cycle phases can be used to calculate the 'relative movement' (RM). By using two different relative movements [RM(t)] extracted from the different BrdUrd pulse-labeling time, the DNA synthesis time (T s ) of the cancer cells can be calculated according to the methods previously described (24)(25)(26): Western blot analysis. Total protein (20 μg/lane) extracted from 1x10 7 cells was separated by 12.5% SDS polyacrylamide gels and transferred onto PVDF membrane with TE77 PWR semi-dry transfer unit.…”

Agaricus blazei Murill enhances doxorubicin-induced apoptosis in human hepatocellular carcinoma cells by NFκB-mediated increase of intracellular doxorubicin accumulation

“…Many studies have demonstrated that polysaccharides from basidiomycetes mushrooms had highly beneficial therapeutic effects including: i) preventing oncogenesis after the administration of peroral medications developed these mushrooms or their extracts, ii) direct anti-tumor activity against various tumors, iii) synergistic anti-tumor activity in combination with chemotherapy, and iv) preventive effects on tumor metastasis (13)(14)(15)(16). Data on polysaccharides isolated from Agaricus blazei Murill (ABM) are highly impressive, and these polysaccharides show promise for use as cancer therapeutics.…”