Expression of BCL-2 Oncoprotein and P53 Protein Accumulation in Bone Marrow Metastases of Androgen Independent Prostate Cancer

McDonnel, Timothy J.; Navone, Nora M.; Troncoso, Patricia; Pisters, Louis L.; Conti, Claudio J.; Eschenbach, Andrew C. von; Brisbay, Shawn; Logothetis, Christopher J.

doi:10.1016/s0022-5347(01)65204-2

Cited by 118 publications

(33 citation statements)

References 17 publications

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“…26) In most androgen-independent prostate cancers, over-expression of Bcl-2 can be observed. 27,28) Bcl-2 expression is also significantly enhanced in early prostate cancers. 29) In preclinical prostate cancer models, inhibition of Bcl-2 expression potentiated the chemotherapeutic effect by increasing apoptosis in the prostate cancer cells.…”

Section: Discussionmentioning

confidence: 96%

Amygdalin Induces Apoptosis through Regulation of Bax and Bcl-2 Expressions in Human DU145 and LNCaP Prostate Cancer Cells

Chang

Shin

Yang

et al. 2006

Biological & Pharmaceutical Bulletin

171

107

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Amygdalin (vitamin B 17 ; previously called laetrile) is one of many nitrilosides, which are natural cyanide-containing substances abundant in the seeds of prunasin family, plant such as apricots, almonds, peaches, apples, and other rosaceous plants. Among the prunasins, Armeniacae semen has been used for the treatment of asthma, bronchitis, emphysema, leprosy, colorectal cancer, leucoderma, and pain. [1][2][3] Amygdalin is composed of two molecules of glucose, one of benzaldehyde, which induces an analgesic action, and one of hydrocyanic acid, which is an anti-neoplastic compound. Apart from the above indications, amygdalin has been used to treat cancers and relieve pain. [4][5][6] In particular, D-amygdalin (D-mandelonitrile-b-D-gentiobioside) is known to exhibit selective killing effect on cancer cells. 7)Prostate cancer is one of the most common non-skin cancers in men. This malignant tumor most often arises in the outer part of the prostate, and as the tumor grows it metastasizes to the tissues around the prostate or into the seminal vesicles. 8)Apoptosis, also known as programmed cell death, occurs in several pathological situations in multicellular organisms and constitutes part of a common mechanism of cell replacement, tissue remodeling, and removal of damaged cells. Apoptosis is a complex process characterized by cell shrinkage, chromatin condensation, internucleosomal DNA fragmentation, and formation of "apoptotic bodies." 9) Two important groups of proteins involved in apoptotic cell death are the members of the Bcl-2 family 10) and a class of cysteine proteases known as caspases.11) The Bcl-2 family can be classified into two functionally distinct groups: antiapoptotic proteins and pro-apoptotic proteins. Bcl-2, an antiapoptotic protein, is known to regulate apoptotic pathways and protects against cell death. Bax, a pro-apoptotic protein of that family, is expressed abundantly and selectively during apoptosis and promotes cell death. Increasing the ratio of Bcl-2 to Bax has commonly been used to determine the induction of apoptosis in several tissues.12) The caspases are aspartate-specific cysteine proteases that have emerged as the central executioner of apoptosis. Among the caspases, activation of caspase-3 is regarded as primary mechanism of apoptosis. 11,13) Caspase-3 can be activated through cytosolic release of cytochrome c by Bax protein. 14)Numerous studies have documented that induction of apoptosis is a very important mechanism in the spontaneous regression of tumors and in the development of anti-tumor agents.15) Apoptosis of tumor cells contributes to the tumor reduction and promotes tumor regression.16) Moreover, anticancer drugs are known to induce apoptosis of tumor cells by damaging their DNA, inhibiting DNA synthesis, depleting intracellular nucleotide pool, and disrupting mitotic apparatus. 17,18) In the present study, we prepared the aqueous extract of the amygdalin from Armeniacae semen and investigated whether this extract induces apoptotic cell death in human DU145 and LNCaP p...

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Section: Discussionmentioning

confidence: 96%

Amygdalin Induces Apoptosis through Regulation of Bax and Bcl-2 Expressions in Human DU145 and LNCaP Prostate Cancer Cells

Chang

Shin

Yang

et al. 2006

Biological & Pharmaceutical Bulletin

171

107

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“…Overexpression of Bcl-2 was observed in most of human neoplastic cells and was found in 40–80% cases of breast (Aggarwal et al, 2007), prostate (McDonnell et al, 1997), lung (Ohmura et al, 2000) and neuroendocrine tumors (Brambilla et al, 1996). It was suggested that a flavonoid-mediated effect could contribute to the decrease of Bcl-2 in neoplastic cells (Shim et al, 2007; Shukla and Gupta, 2004).…”

Section: Discussionmentioning

confidence: 99%

The tetramethoxyflavone zapotin selectively activates protein kinase C epsilon, leading to its down-modulation accompanied by Bcl-2, c-Jun and c-Fos decrease

Totoń¹,

Lisiak²,

Rubiś³

et al. 2012

European Journal of Pharmacology

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Zapotin, a tetramethoxyflavone, is a natural compound with a wide spectrum of activities in neoplastic cells. Protein kinase C epsilon (PKCε) has been shown to be oncogenic, with the ability to increase cell migration, invasion and survival of tumor cells. Here we report that zapotin inhibits cell proliferation. In wild-type HeLa cells with basal endogenous expression of PKCε, the IC50 was found to be 17.9 ± 1.6 μM. In HeLa cells overexpressing doxycycline-inducible constitutively active PKCε (HeLaPKCεA/E), the IC50 was 7.6 ± 1.3 μM, suggesting that PKCε enhances the anti-proliferative effect of zapotin. Moreover, we found that zapotin selectively activated PKCε in comparison with other PKC family members, but attenuated doxycycline-induced PKCε expression. As a result of zapotin treatment for 6, 12 and 24 h, the doxycycline-induced levels of the two differently phosphorylated PKCε forms (87 kDa and 95 kDa) were decreased. Migration assays revealed that increasing concentrations of zapotin (from 3.5 to 15 μM) decreased migration of HeLaPKCεA/E cells. Furthermore, zapotin significantly increased the fraction of apoptotic cells in doxycycline-induced (HeLaPKCεA/E) cells after 24 h and decreased the levels of Bcl-2, c-Jun, c-Fos. This was accompanied by a degradation of PARP-1. In summary, activation of PKCε and down-modulation of the induced PKCε level by zapotin were associated with decreased migration and increased apoptosis. These observations are consistent with the previously reported chemopreventive and chemotherapeutic action of zapotin.

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“…Finally, advances in our understanding of the relationship between androgenwithdrawal and the onset of apoptosis of prostate cancer cells have also led to intense study as to whether gene products that mediate the apoptotic process might also be involved in the generation of therapeutic resistance of prostate cancer. As a result of these studies, we now know that the bcl-2 protein, a potent inhibitor of apoptosis, is frequently overexpressed in hormone resistant human prostate cancers (Raffo et al, 1995;Krajewski et al, 1996;McDonnell et al, 1997). Institutional surveys of hormone-resistant human prostate cancers for bcl-2 overexpression have found differing prevalence of this biomarker, ranging from 35 to over 60% of such specimens analysed Furuya et al, 1996;McDonnell et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

“…As a result of these studies, we now know that the bcl-2 protein, a potent inhibitor of apoptosis, is frequently overexpressed in hormone resistant human prostate cancers (Raffo et al, 1995;Krajewski et al, 1996;McDonnell et al, 1997). Institutional surveys of hormone-resistant human prostate cancers for bcl-2 overexpression have found differing prevalence of this biomarker, ranging from 35 to over 60% of such specimens analysed Furuya et al, 1996;McDonnell et al, 1997). Again, these numbers fail to account for all cases of hormone resistant prostate cancer and it is imperative that the search for the genetic basis of hormone (and other therapeutic) resistance in prostate cancers be continued.…”

Section: Introductionmentioning

confidence: 99%

The emergence of protocadherin-PC expression during the acquisition of apoptosis-resistance by prostate cancer cells

et al. 2002

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Expression of BCL-2 Oncoprotein and P53 Protein Accumulation in Bone Marrow Metastases of Androgen Independent Prostate Cancer

Cited by 118 publications

References 17 publications

Amygdalin Induces Apoptosis through Regulation of Bax and Bcl-2 Expressions in Human DU145 and LNCaP Prostate Cancer Cells

Amygdalin Induces Apoptosis through Regulation of Bax and Bcl-2 Expressions in Human DU145 and LNCaP Prostate Cancer Cells

The tetramethoxyflavone zapotin selectively activates protein kinase C epsilon, leading to its down-modulation accompanied by Bcl-2, c-Jun and c-Fos decrease

The emergence of protocadherin-PC expression during the acquisition of apoptosis-resistance by prostate cancer cells

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