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Cucurbitacin B Causes Increased Radiation Sensitivity of Human Breast Cancer Cells via G2/M Cell Cycle Arrest.

Duangmano S, Sae-Lim P, Suksamrarn A, Patmasiriwat P, Domann FE - J Oncol (2012)

Bottom Line: Results.Flow cytometric analysis for DNA content indicated that cucurbitacin B resulted in G2/M arrest in MDA-MB-231 and MCF7:5C but not SKBR-3 cells.Therefore, combinations of cucurbitacin B with radiotherapy may be appropriate for experimental breast cancer treatment.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.

ABSTRACT
Purpose. To explore the effects of cucurbitacin B on the radiation survival of human breast cancer cells and to elucidate the cellular mechanism of radiosensitization if any. Materials and Methods. Human breast carcinoma cell lines were treated with cucurbitacin B before irradiation with 0-10 Gy of (137)Cs gamma rays. The effect of cucurbitacin B on cell-survival following irradiation was evaluated by colony-forming assay. Cell cycle distributions were investigated using flow cytometry. Real-time PCR and western blots were performed to investigate the expression of cell cycle checkpoints. Results. Cucurbitacin B inhibited breast cancer cell proliferation in a dose-dependent manner. Only MDA-MB-231 and MCF7:5C cells but not SKBR-3 cells were radiosensitized by cucurbitacin B. Flow cytometric analysis for DNA content indicated that cucurbitacin B resulted in G2/M arrest in MDA-MB-231 and MCF7:5C but not SKBR-3 cells. Moreover, Real-time PCR and western blot analysis demonstrated upregulated p21 expression before irradiation, a likely cause of the cell cycle arrest. Conclusion. Taken together, these findings suggest that cucurbitacin B causes radiosensitization of some breast cancer cells, and that cucurbitacin B induced G2/M arrest is an important mechanism. Therefore, combinations of cucurbitacin B with radiotherapy may be appropriate for experimental breast cancer treatment.

No MeSH data available.


Related in: MedlinePlus

Structure of cucurbitacin B.
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sch1: Structure of cucurbitacin B.

Mentions: Breast cancer is now the most common cause of female cancer and leading cause of cancer deaths among women in the United States and many other parts of the world [1, 2]. Over the past several decades, the incidence of breast cancer has been increasing in economically developed countries [3]. Human epidermal growth factor receptor 2 (Her2) and Estrogen receptor (ER) play critical roles in the development and progression of breast cancer. About 80% of breast cancers are hormone-receptors positive and express estrogen receptors [4]. About 20% of breast cancers do not express estrogen receptor and also Her2 [5, 6]. Therefore, breast cancer that negative for ER and Her2 does not respond to hormonal therapy. Current therapies for the treatment of breast cancer may result in drug resistance or toxicity. There is growing interest in the use of herbs to aid in the maintenance of women's health; it is interesting to use of herbs for the women's health care. Plants contain a wide variety of chemicals that have potent biological effects, including anticancer activity. Natural cucurbitacins are highly oxygenated, tetracyclic triterpenes containing the cucurbitane nucleus skeleton and are predominantly found in plants of the family cucurbitaceae, members of which have long been used in oriental medicines because of the wide range biological activity they exhibited in plants and animals. Among the various cucurbitacins, the most abundant is cucurbitacin B. Cucurbitacin B (Scheme 1) extracted from the Thai herb Trichosanthes cucumerina L. has been shown to have anticancer, antimicrobial, and anti-inflammatory activities [7, 8]. Several studies reported that cucurbitacin B and its relatives inhibit the growth of human malignant cells both in vitro and in vivo including breast cancer [9], head and neck squamous cell carcinoma [10], pancreatic cancer [11], hepatocellular carcinoma [12], osteosarcoma [13], and myeloid leukemia [14]. Our previous report has shown that cucurbitacin B exerts anticancer effect by inhibiting telomerase via downregulating both the hTERT and c-Myc expression and arrest of the cell cycle at G2/M phase in breast cancer cells [15]. Some studies have reported that cells are most sensitive to radiation in G2/M and most resistant in S phase [16]. For example, synchronized Chinese hamster cells were most sensitive to irradiation during mitosis and in G2 phase and less sensitive in G1 and the latter past of S phase [17, 18]. Drugs, including Docetaxel, that arrest cells cell in G2/M phase of cell cycle have been demonstrated as radiosensitizer agent [19]. The aims of this study were to determine the radiosensitizing potential of cucurbitacin B in human breast cancer cells and to elucidate the cellular mechanism of the radiosensitization. In the present study, we demonstrated that cucurbitacin B sensitizes human breast cancer cells to radiation by inducing them to accumulate in G2/M phase of the cell cycle.


Cucurbitacin B Causes Increased Radiation Sensitivity of Human Breast Cancer Cells via G2/M Cell Cycle Arrest.

Duangmano S, Sae-Lim P, Suksamrarn A, Patmasiriwat P, Domann FE - J Oncol (2012)

Structure of cucurbitacin B.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368438&req=5

sch1: Structure of cucurbitacin B.
Mentions: Breast cancer is now the most common cause of female cancer and leading cause of cancer deaths among women in the United States and many other parts of the world [1, 2]. Over the past several decades, the incidence of breast cancer has been increasing in economically developed countries [3]. Human epidermal growth factor receptor 2 (Her2) and Estrogen receptor (ER) play critical roles in the development and progression of breast cancer. About 80% of breast cancers are hormone-receptors positive and express estrogen receptors [4]. About 20% of breast cancers do not express estrogen receptor and also Her2 [5, 6]. Therefore, breast cancer that negative for ER and Her2 does not respond to hormonal therapy. Current therapies for the treatment of breast cancer may result in drug resistance or toxicity. There is growing interest in the use of herbs to aid in the maintenance of women's health; it is interesting to use of herbs for the women's health care. Plants contain a wide variety of chemicals that have potent biological effects, including anticancer activity. Natural cucurbitacins are highly oxygenated, tetracyclic triterpenes containing the cucurbitane nucleus skeleton and are predominantly found in plants of the family cucurbitaceae, members of which have long been used in oriental medicines because of the wide range biological activity they exhibited in plants and animals. Among the various cucurbitacins, the most abundant is cucurbitacin B. Cucurbitacin B (Scheme 1) extracted from the Thai herb Trichosanthes cucumerina L. has been shown to have anticancer, antimicrobial, and anti-inflammatory activities [7, 8]. Several studies reported that cucurbitacin B and its relatives inhibit the growth of human malignant cells both in vitro and in vivo including breast cancer [9], head and neck squamous cell carcinoma [10], pancreatic cancer [11], hepatocellular carcinoma [12], osteosarcoma [13], and myeloid leukemia [14]. Our previous report has shown that cucurbitacin B exerts anticancer effect by inhibiting telomerase via downregulating both the hTERT and c-Myc expression and arrest of the cell cycle at G2/M phase in breast cancer cells [15]. Some studies have reported that cells are most sensitive to radiation in G2/M and most resistant in S phase [16]. For example, synchronized Chinese hamster cells were most sensitive to irradiation during mitosis and in G2 phase and less sensitive in G1 and the latter past of S phase [17, 18]. Drugs, including Docetaxel, that arrest cells cell in G2/M phase of cell cycle have been demonstrated as radiosensitizer agent [19]. The aims of this study were to determine the radiosensitizing potential of cucurbitacin B in human breast cancer cells and to elucidate the cellular mechanism of the radiosensitization. In the present study, we demonstrated that cucurbitacin B sensitizes human breast cancer cells to radiation by inducing them to accumulate in G2/M phase of the cell cycle.

Bottom Line: Results.Flow cytometric analysis for DNA content indicated that cucurbitacin B resulted in G2/M arrest in MDA-MB-231 and MCF7:5C but not SKBR-3 cells.Therefore, combinations of cucurbitacin B with radiotherapy may be appropriate for experimental breast cancer treatment.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.

ABSTRACT
Purpose. To explore the effects of cucurbitacin B on the radiation survival of human breast cancer cells and to elucidate the cellular mechanism of radiosensitization if any. Materials and Methods. Human breast carcinoma cell lines were treated with cucurbitacin B before irradiation with 0-10 Gy of (137)Cs gamma rays. The effect of cucurbitacin B on cell-survival following irradiation was evaluated by colony-forming assay. Cell cycle distributions were investigated using flow cytometry. Real-time PCR and western blots were performed to investigate the expression of cell cycle checkpoints. Results. Cucurbitacin B inhibited breast cancer cell proliferation in a dose-dependent manner. Only MDA-MB-231 and MCF7:5C cells but not SKBR-3 cells were radiosensitized by cucurbitacin B. Flow cytometric analysis for DNA content indicated that cucurbitacin B resulted in G2/M arrest in MDA-MB-231 and MCF7:5C but not SKBR-3 cells. Moreover, Real-time PCR and western blot analysis demonstrated upregulated p21 expression before irradiation, a likely cause of the cell cycle arrest. Conclusion. Taken together, these findings suggest that cucurbitacin B causes radiosensitization of some breast cancer cells, and that cucurbitacin B induced G2/M arrest is an important mechanism. Therefore, combinations of cucurbitacin B with radiotherapy may be appropriate for experimental breast cancer treatment.

No MeSH data available.


Related in: MedlinePlus