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      β-Bourbonene attenuates proliferation and induces apoptosis of prostate cancer cells

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          Abstract

          Sesquiterpenes have antitumor, anti-inflammation, and anti-fungal effects. β-bourbonene is a kind of sesquiterpene, but its pharmacological effect has not been studied. The present study was conducted in order to investigate the potential anticancer effects of β-bourbonene on human prostate cancer PC-3M cells. PC-3M cells were incubated with 0, 25, 50, 100 µg/ml of β-bourbonene. Cell Counting Kit-8 (CCK-8) detection showed that compared with the control group, β-bourbonene inhibited the growth of PC-3M cells in a dose-dependent manner. G0/G1 phase arrest was observed by β-bourbonene by using flow cytometry. TUNEL staining and Annexin V/PI dual-staining method revealed that apoptosis was found in cells with β-bourbonene treatment, and the quantity of apoptotic cells was increased with the elevation in concentration. The mRNA and protein expression levels of Fas and FasL in the drug-treatment group were significantly elevated. Furthermore, the western blot assay also indicated that with an increase in the concentration of β-bourbonene, the protein expression of Bax in the drug-treatment group was significantly elevated, while a decrease was identified in the protein expression of Bcl-2. Taken together, β-bourbonene can inhibit the proliferation and simultaneously, induce apoptosis and G0/G1 arrest of prostate cancer PC-3M cells, which may be realized by upregulation of mRNA expression of Fas and FasL, increase of Bax protein expression and decrease of Bcl-2 protein expression.

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          Most cited references20

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          Cancer Statistics, 2008

          Each year, the American Cancer Society estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. Incidence and death rates are age-standardized to the 2000 US standard million population. A total of 1,437,180 new cancer cases and 565,650 deaths from cancer are projected to occur in the United States in 2008. Notable trends in cancer incidence and mortality include stabilization of incidence rates for all cancer sites combined in men from 1995 through 2004 and in women from 1999 through 2004 and a continued decrease in the cancer death rate since 1990 in men and since 1991 in women. Overall cancer death rates in 2004 compared with 1990 in men and 1991 in women decreased by 18.4% and 10.5%, respectively, resulting in the avoidance of over a half million deaths from cancer during this time interval. This report also examines cancer incidence, mortality, and survival by site, sex, race/ethnicity, education, geographic area, and calendar year, as well as the proportionate contribution of selected sites to the overall trends. Although much progress has been made in reducing mortality rates, stabilizing incidence rates, and improving survival, cancer still accounts for more deaths than heart disease in persons under age 85 years. Further progress can be accelerated by supporting new discoveries and by applying existing cancer control knowledge across all segments of the population.
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            Molecular determinants of resistance to antiandrogen therapy.

            Using microarray-based profiling of isogenic prostate cancer xenograft models, we found that a modest increase in androgen receptor mRNA was the only change consistently associated with the development of resistance to antiandrogen therapy. This increase in androgen receptor mRNA and protein was both necessary and sufficient to convert prostate cancer growth from a hormone-sensitive to a hormone-refractory stage, and was dependent on a functional ligand-binding domain. Androgen receptor antagonists showed agonistic activity in cells with increased androgen receptor levels; this antagonist-agonist conversion was associated with alterations in the recruitment of coactivators and corepressors to the promoters of androgen receptor target genes. Increased levels of androgen receptor confer resistance to antiandrogens by amplifying signal output from low levels of residual ligand, and by altering the normal response to antagonists. These findings provide insight toward the design of new antiandrogens.
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              bcl-2: role in epithelial differentiation and oncogenesis.

              The precise regulation and maintenance of balance between cell proliferation and cell death in multicellular organisms is critical for tissue homeostasis. bcl-2 initiates a new gene family involved in the regulation of cell death and survival without affecting cell proliferation. Expression of Bcl-2 has been reported in a wide range of hematopoietic cells, nonneoplastic epithelia (both hormone-responsive and nonresponsive), and epithelial malignancies. Although the major group of epithelial cells expressing Bcl-2 protein are in the proliferating zones, expression is not directly related to cell proliferation. Bcl-2 is also associated with stem cells committed to differentiation and morphogenesis. The survival advantage provided by Bcl-2 prolongs the life span of epithelial cells with differentiation potential and allows proliferation, differentiation, and morphogenesis to proceed. The gene expression in hormone-responsive organs may contribute to the sustained life of those terminally differentiated epithelial cells and a decrease in Bcl-2 levels leads to cell death by apoptosis. Overexpression of bcl-2 protects epithelial cells from death, but it is neither able to immortalize normal cells, nor to cause tumorigenic transformation of immortalized epithelial cells. Heterogeneous expression of Bcl-2 in epithelial malignancies suggests that the gene is differentially regulated. Furthermore, its expression in association with precancerous lesions suggests a role in the early stage of tumorigenesis. The effects of Bcl-2 expression on sensitivity of epithelial cells to drug, radiation, and hormone therapies vary depending on the typed of tumor. Expression of Bcl-2 is associated with resistance to hormone therapy and recurrence in prostate carcinomas, whereas in lung and breast carcinomas it is associated with a better prognosis. Studies now being performed should clarify the underlying mechanisms of differential gene regulation in different tissues and show the clinical significance of the expression of bcl-2 and other members of the bcl-2 gene family.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                October 2018
                20 July 2018
                20 July 2018
                : 16
                : 4
                : 4519-4525
                Affiliations
                Department of Urology, Sixth People's Hospital South Campus Affiliated to Shanghai Jiaotong University, Shanghai 201499, P.R. China
                Author notes
                Correspondence to: Dr Ji-Zhong Jin, Department of Urology, Sixth People's Hospital South Campus Affiliated to Shanghai Jiaotong University, 6600 Nanfeng Road, Shanghai 201499, P.R. China, E-mail: jinjizhong1016@ 123456163.com
                Article
                OL-0-0-9183
                10.3892/ol.2018.9183
                6126340
                30197674
                409bb6d8-f99b-4f6a-8563-2f36948e185e
                Copyright: © Wang et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 02 September 2017
                : 12 July 2018
                Categories
                Articles

                Oncology & Radiotherapy
                β-bourbonene,pc-3m,proliferation,cell cycle,apoptosis,fas/fasl,bax/bcl-2
                Oncology & Radiotherapy
                β-bourbonene, pc-3m, proliferation, cell cycle, apoptosis, fas/fasl, bax/bcl-2

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