Cucurbitacin B induces differentiation, cell cycle arrest, and actin cytoskeletal alterations in myeloid leukemia cells

Haritunians, Talin; Gueller, Saskia; Zhang, Ling; Badr, Riem; Ding, Yin; Xing, Hongtao; Fung, Ming Chiu; Koeffler, H. Phillip

doi:10.1016/j.leukres.2008.01.019

Cited by 67 publications

(50 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This active ingredient has antiproliferative effects on several types of malignancies and is known to be an dual inhibitor of the activation of both JAK2 and STAT3 in some malignancies (3). Recently, we were able to show that cucurbitacin B has antiproliferative activity against human breast cancer, glioblastoma multiforme, and myeloid leukemia cells (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Cucurbitacin B Induces Apoptosis by Inhibition of the JAK/STAT Pathway and Potentiates Antiproliferative Effects of Gemcitabine on Pancreatic Cancer Cells

Thoennissen

Iwanski²,

Doan³

et al. 2009

Cancer Research

Self Cite

221

183

View full text Add to dashboard Cite

Pancreatic cancer is an aggressive malignancy that is generally refractory to chemotherapy, thus posing experimental and clinical challenges. In this study, the antiproliferative effect of the triterpenoid compound cucurbitacin B was tested in vitro and in vivo against human pancreatic cancer cells. Dose-response studies showed that the drug inhibited 50% growth of seven pancreatic cancer cell lines at 10 À7 mol/L, whereas clonogenic growth was significantly inhibited at 5 Â 10 À8 mol/L. Cucurbitacin B caused dose-and timedependent G 2 -M-phase arrest and apoptosis of pancreatic cancer cells. This was associated with inhibition of activated JAK2, STAT3, and STAT5, increased level of p21 WAF1 even in cells with nonfunctional p53, and decrease of expression of cyclin A, cyclin B1, and Bcl-XL with subsequent activation of the caspase cascade. Interestingly, the combination of cucurbitacin B and gemcitabine synergistically potentiated the antiproliferative effects of gemcitabine on pancreatic cancer cells. Moreover, cucurbitacin B decreased the volume of pancreatic tumor xenografts in athymic nude mice by 69.2% (P < 0.01) compared with controls without noticeable drug toxicities. In vivo activation of JAK2/STAT3 was inhibited and expression of Bcl-XL was decreased, whereas caspase-3 and caspase-9 were up-regulated in tumors of drug-treated mice. In conclusion, we showed for the first time that cucurbitacin B has profound in vitro and in vivo antiproliferative effects against human pancreatic cancer cells, and the compound may potentate the antiproliferative effect of the chemotherapeutic agent gemcitabine. Further clinical studies are necessary to confirm our findings in patients with pancreatic cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

Cucurbitacin B Induces Apoptosis by Inhibition of the JAK/STAT Pathway and Potentiates Antiproliferative Effects of Gemcitabine on Pancreatic Cancer Cells

Thoennissen

Iwanski²,

Doan³

et al. 2009

Cancer Research

Self Cite

221

183

View full text Add to dashboard Cite

show abstract

“…CuB also caused a G2-M cell cycle arrest in laryngeal squamous cell carcinoma cells, glioblastoma multiforme cells, and pancreatic cancer cells (12,14,15). In contrast, CuB induced a S phase arrest of leukemia cells and hepatocellular carcinoma cells (10,16). The explanation for these differences is unclear.…”

Section: Discussionmentioning

confidence: 97%

“…Previous studies from our group demonstrated CuB can disrupt F-actins and microtubules in glioma, leukemia, as well as breast cancer cells (15,16,18). Given that the F-actin and the microtubule cytoskeleton is a key component involved in cell migration, we tested the ability of CuB to affect cell migration and found that CuB inhibited migration of CSCC cells.…”

Section: Discussionmentioning

confidence: 97%

“…In modern medicine, its anti-proliferative potential is of particular interest, which have been studied in leukemia and a variety of solid tumors (10,12,(14)(15)(16)18). In this study, we examined for the first time the anti-proliferative effect of CuB against CSCC cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have suggested that CuB inhibits the growth of numerous human cancer cell lines and tumor xenografts, including leukemias, lymphomas, multiple myelomas, melanomas and cancers of oral cavity, nasopharynx, breast, prostate, lung, uterine cervix, liver, and brain (10,11,13). The anti-tumor mechanism of CuB involves a variety of effects including induction of apoptosis, and/or differentiation, arrest of the cell cycle, disruption of the cytoskeleton as well as interruption of several signal transduction pathways (14)(15)(16)(17). However, the effect of CuB and its underlying mechanism of action against CSCC are unexplored.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cucurbitacin B inhibits growth, arrests the cell cycle, and potentiates antiproliferative efficacy of cisplatin in cutaneous squamous cell carcinoma cell lines

Yin¹

2010

Int J Oncol

View full text Add to dashboard Cite

Abstract. Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer with a substantial risk of metastasis which causes clinical treatment failure. This study investigated the anti-CSCC effects of a triterpenoid compound, Cucurbitacin B (CuB). Dose-response studies showed that CuB inhibited 50% growth (ED 50 ) of the CSCC cell lines (SRB1, SRB12, SCC13, COLO16) in liquid culture at 4x10 -7 -10 -5 M. Soft-agar assays demonstrated that nearly all of the CSCC clonogenic cells were inhibited at 10 -7 M CuB. FACS analysis found that the compound (10 -7 M, 48 h) caused G2/M arrest. The CSCC cells underwent profound morphologic changes within 60 min after exposure to CuB (10 -7 M), rounding up and losing their pseudopodia. CuB (10 -7 M) caused prominent multinucleation of the cells after they were pulse-exposed (24 h) to the drug, washed and cultured in normal medium for an additional 24 h. The drug (10 -8 -10 -6 M, 3-24 h) decreased levels of CDC2 and cyclin B1 in SRB1 and SRB12 cell lines as seen by Western blot analysis. Migration of SRB1 and SRB12 cells was inhibited by 10 -7 M CuB. Interestingly, CuB synergistically potentiated the anti-proliferative effect of cisplatin in CSCC. In summary, CuB has a prominent anti-proliferative activity on CSCC cells. In vivo studies and clinical trials of this drug should be pursued in CSCC.

show abstract

The triterpenoid cucurbitacin B augments the antiproliferative activity of chemotherapy in human breast cancer

Aribi

Gery

Lee

et al. 2012

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Despite recent advances in therapy, breast cancer remains the second most common cause of death from malignancy in women. Chemotherapy plays a major role in breast cancer management, and combining chemotherapeutic agents with non-chemotherapeutic agents is of considerable clinical interest. Cucurbitacins are triterpenes compounds found in plants of the Cucurbitaceae family, reported to have anti-cancer and anti-inflamatory activities. Previously, we have shown antiproliferative activity of cucurbitacin B (CuB) in breast cancer, and we hypothesized that combining CuB with chemotherapeutic agents can augment their anti-tumor effect. Here, we show that a combination of CuB with either docetaxel (DOC) or gemcitabine (GEM) synergistically inhibited the proliferation of MDA-MB-231 breast cancer cells in vitro. This antiproliferative effect was accompanied by an increase in apoptosis rates. Furthermore, in vivo treatment of human breast cancer orthotopic xenografts in immunodeficient mice with CuB at either low (0.5 mg/kg) or high (1 mg/kg) doses in combination with either DOC (20 mg/kg) or GEM (12.5 mg/kg) significantly reduced tumor volume as compared to monotherapy of each drug. Importantly, no significant toxicity was noted with low dose CuB in combination with either DOC or GEM. In conclusion, combination of CuB at a relatively low concentration with either of the chemotherapeutic agents, DOC or GEM, shows prominent antiproliferative activity against breast cancer cells without increased toxicity. This promising combination should be examined in therapeutic trials of breast cancer.

show abstract

Cucurbitacin B induces differentiation, cell cycle arrest, and actin cytoskeletal alterations in myeloid leukemia cells

Cited by 67 publications

References 16 publications

Cucurbitacin B Induces Apoptosis by Inhibition of the JAK/STAT Pathway and Potentiates Antiproliferative Effects of Gemcitabine on Pancreatic Cancer Cells

Cucurbitacin B Induces Apoptosis by Inhibition of the JAK/STAT Pathway and Potentiates Antiproliferative Effects of Gemcitabine on Pancreatic Cancer Cells

Cucurbitacin B inhibits growth, arrests the cell cycle, and potentiates antiproliferative efficacy of cisplatin in cutaneous squamous cell carcinoma cell lines

The triterpenoid cucurbitacin B augments the antiproliferative activity of chemotherapy in human breast cancer

Contact Info

Product

Resources

About