Cytotoxicity enhancement in MDA-MB-231 cells by the combination treatment of tetrahydropalmatine and berberine derived from Corydalis yanhusuo W. T. Wang

Abstract

Aim:Our previous works have demonstrated that Chinese herb medicine yanhusuo (Corydalis yanhusuo W. T. Wang) has strong anti-cancer proliferation effect in MDA-MB-231 cells. The goal of this study was to find out the synergic cytotoxicity effect of three natural compounds, tetrahydropalmatine (THP), berberine (Ber), and dehydrocorydaline (DHC), isolated from C. yanhusuo W. T. Wang.Materials and Methods:The IC50 of THP Ber and DHC in single use, as well as in combination use at fixed ratios and doses was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. Isobologram, combination index and modified coefficient of drug interaction (CDI) methods were used for evaluation the combination effects of THF! Ber, and DHC in different ratio and concentration.Results:The results indicated that the combination of THP and Ber shown the strongest anti-cancer cell proliferation effect at the ratio of 2:3 (Ber: THF the average CDI value was 0.5795). DHC and THP have additive cytotoxicity in MDA-MB-231 cells. However, there wasn’t any synergistic effect between Ber and DHC, and it even exhibited antagonistic effect when the percentage of DHC was >50%.Conclusion:Our findings suggested that the combination of THP and Ber might be beneficial for anti-proliferation of MDA-MB-231 breast cancer cells through a significant synergy effect.

LKB1 promotes metabolic flexibility in response to energy stress

“…However, treatment with both phenformin and BPTES yielded significant impacts on cellular viability, with LKB1-deficient cell lines being most sensitive (Figure 5D). Combination index and coefficient of drug interaction (CDI) were calculated to assess potential synergistic effects of phenformin and BPTES on cell viability, where CDI <0.7 indicates a significant synergy (Zhao et al, 2014). Strikingly, we observed that combination treatment with phenformin and BPTES yielded a synergistic response more so in LKB1-deficient cells (Figure 5E).…”

“…Given the decreased plasticity of LKB1-deficient cells, we investigated whether combination treatments using phenformin and a glutaminase inhibitor would enhance the cell-killing effects in these cell populations. We observed that BPTES and phenformin synergistically decreased NSCLC cell survival, as evidenced by coefficient of drug interaction (CDI) scores <0.7 in A549 and H460 cell lines (Zhao et al, 2014). Strikingly, LKB1-deficient A549 and H460 cells were significantly more sensitive to combination treatment with phenformin and BPTES compared to LKB1-proficient cells.…”

“…Drug synergism was determined using the combination index (CI) and coefficient of drug interaction (CDI) methods (Hao et al, 2008; Zhao et al, 2014). CI was quantified by calculating the ratio of response compared to vehicle treatment for each single treatment.…”

“…CDI < 1 suggests drugs are synergistic and CDI < 0.7 indicates that combination drug treatment is significantly synergistic (Zhao et al, 2014). …”

Application of UPLC‐MS/MS to simultaneously detect four bioactive compounds in the tumour‐shrinking decoction (FM1523) for uterine fibroids treatment

“…Lin et al confirmed that tetrahydropalmatine is the primary ingredient of Corydalis Rhizoma . Importantly, tetrahydropalmatine has anti‐MDR effect on MCF‐7 cell lines, and could enhance the ability to inhibit the proliferation of human leukemia cell lines by combining with vincristine . Another 11 medicines show similar effects.…”