Panduratin A Inhibits Cell Proliferation by Inducing G0/G1 Phase Cell Cycle Arrest and Induces Apoptosis in Breast Cancer Cells

Because of the unsatisfactory treatment options for breast cancer (BC), there is a need to develop novel therapeutic approaches for this malignancy. One such strategy is chemotherapy using non-toxic dietary substances and botanical products. Studies have shown that Panduratin A (PA) possesses many health benefits, including anti-inflammatory, anti-bacterial, anti-oxidant and anti-cancer activities. In the present study, we provide evidence that PA treatment of MCF-7 BC cells resulted in a time- and dose-dependent inhibition of cell growth with an IC50 of 15 µM and no to little effect on normal human MCF-10A breast cells. To define the mechanism of these anti-proliferative effects of PA, we determined its effect critical molecular events known to regulate the cell cycle and apoptotic machinery. Immunofluorescence and flow cytometric analysis of Annexin V-FITC staining provided evidence for the induction of apoptosis. PA treatment of BC cells resulted in increased activity/expression of mitochondrial cytochrome C, caspases 7, 8 and 9 with a significant increase in the Bax:Bcl-2 ratio, suggesting the involvement of a mitochondrial-dependent apoptotic pathway. Furthermore, cell cycle analysis using flow cytometry showed that PA treatment of cells resulted in G0/G1 arrest in a dose-dependent manner. Immunoblot analysis data revealed that, in MCF-7 cell lines, PA treatment resulted in the dose-dependent (i) induction of p21WAF1/Cip1 and p27Kip1, (ii) downregulation of Cyclin dependent kinase (CDK) 4 and (iii) decrease in cyclin D1. These findings suggest that PA may be an effective therapeutic agent against BC.

Analysis of influence factors on neoadjuvant chemotherapy efficacy in inflammatory breast cancer / 中国医师进修杂志

Objective To explore the relationship of molecular biology characteristic and the treatment outcome,and influence factors of neoadjuvant chemotherapy (NAC) in inflammatory breast cancer (IBC).Methods The clinicopathological data of 103 IBC patients who were treated with NAC from January 2005 to June 2013 were analyzed retrospectively.Immunohistochemical method was used to detect the expression of estrogen receptor (ER),progesteron receptor (PR),human epidermal growth factor receptor 2 (HER-2) and E-cadherin.The treatment outcome were evaluated.Results In 103 IBC patients,ER negative was 48 patients,PR negative was 51 patients,HER-2 positive was 45 patients,E-cadherin positive was 66 patients.The effective rate of chemotherapy was 72.8％ (75/103).The effective rate of chemotherapy in taxane-based group was significantly higher than that in anthracycline-based group [80.6％ (50/62) vs.61.0％(25/41)],and there was significant difference (P ＜ 0.05).The effective rate of chemotherapy in ER,PR,E-cadherin negative patients was significantly higher than that in ER,PR,E-cadherin positive patients [83.3％ (40/48) vs.63.6％ (35/55),82.4％ (42/51) vs.63.5％ (33/52),83.8％ (31/37) vs.66.7％ (44/66)],and there was significant difference (P ＜ 0.05).The effective rate of chemotherapy in taxane-based group with E-cadherin positive patients was significantly higher than that in anthracycline-based group with E-cadherin positive patients [77.5％ (31/40) vs.50.0％ (13/26)] (P ＜0.05).No correlation existed between the expression of HER-2 and the treatment outcome of chemotherapy (P ＞ 0.05).Conclusion ER,PR and E-cadherin negative patients with IBC is chemosensitive to NAC.The positive expression of E-cadherin may be an important factor of chemotherapy resistance.For the patients with E-cadherin positive,taxane-based chemotherapy regimen can achieve a better effective rate.

Evaluation of neoadjuvant chemotherapy efficacy by the expression of cyclin D1 in human breast cancer / 肿瘤研究与临床

Objective To evaluate the effect of neoadjuvant chemotherapy (NAC) by investigating the expression of cyclin D1 in human breast cancer before and after NAC.Methods Eighty-four cases of breast cancer were diagnosed by core biopsies.The expression level of cyclin D1 in cancer tissues was measured by immunohistochemical envision two-step method before and after NAC (pirarubicin and docetaxel regimen for 3-4 cycles).Results Complete remission (CR) occurred in 4 cases of 84 patients (4.76 ％) with 2 pathological complete response cases,partial response (PR) in 54 cases (64.29 ％),stability (SD) in 26 cases (30.95 ％) and no disease progression (PD) patients.The positive rate of cyclin D1 in cancer tissues [65.48 ％ (55/84)] was significantly decreased after NAC [39.29 ％ (33/84)] (x2 =11.55,P =0.001).In clinical level,the ease rate was significantly improved in patients whose cyclin D1 expression switched from positive [86.36 ％ (19/22)] to negative [45.45 ％ (15/33)] after NAC treatment (x2 =9.359,P =0.002).Conclusion NAC significantly decreases the expression of cyclin D1 in breast cancer tissues.Meanwhile,the ease rate is improved when cyclin D1 expression switched from positive to negative after NAC.Therefore,cyclin D1 expression can be used as an evaluation index for the efficiency of NAC.

Correlation of ultrasonographic types of breast fibroadenomas with pathologic findings / 中华超声影像学杂志

Objective To explore the correlation of ultrasonographic,pathologic,and clinical findings of breast fibroadenomas.Methods 157 cases of breast fibroadenomas demonstrated by pathologic findings were examined with color Doppler ultrasound prior to biopsy.Images were classified according to ultrasound characteristics and analysed with latter pathologic findings.Results Ultrasound images of 157 cases could be divided into 6 types:uniformity( n =82),linage( n =37),bicolor( n =15),nodule-in-nodule (n =3),cyst-massity mixed ( n =9),calcify( n =11).5 cases were mistakenly judged to breast cancer on ultrasound images(1 ease in the linage,1 case in the cyst-mass mixed,3 cases in the calcify).Accurate ratio of ultrasound diagnosis was 96.82％.Pathologic finding:①Uniformity type,hyperplasia of both the gland and fibrous tissue of tumor in order.② Linage type,hyperplasia fibrous tissue in belt.③ Bicolor type,significant difference in the proportion and arrangement of the hyperplasia gland and fibrous tissue.④Nodule-in-nodule type,extensive hemorrhagic infarction in tumor.⑤Cyst-massity mixed type,hydatoncus,metaplasia in great sweat gland,hyperplasia conduit epithelial,conduit cystic-expansion.⑥ Calcify type,fibroadenomas on growth of static or regression transformation,and calcify of interstitial tissue.Conclusions Ultrasonic diagnosis and its simple typing is an accurate,simple and effective way for the diagnosis of breast fibroadenoma,which may improve the accuracy of diagnosis rate for breast fibroadenoma.It is helpful for choosing the surgical remedies.