Dual Role of Prostratin in Inhibition of Infection and Reactivation of Human Immunodeficiency Virus from Latency in Primary Blood Lymphocytes and Lymphoid Tissue

Biancotto, Angélique; Grivel, Jean‐Charles; Gondois-Rey, Françoise; Bettendroffer, Lise; Vigne, Robert; Brown, Stephen J.; Margolis, Leonid; Hirsch, Ivan

doi:10.1128/jvi.78.19.10507-10515.2004

Cited by 81 publications

(73 citation statements)

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“…HDAC inhibitors do not enhance de novo HIV infection (78). Prostratin restricts viral entry and reverse transcription but facilitates integration of the HIV genome in nondividing CD4 T cells (5). Here, we found that HMBA significantly inhibits HIV-1 infection in PBMCs.…”

Section: Discussionmentioning

confidence: 51%

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Hexamethylbisacetamide Remodels the Human Immunodeficiency Virus Type 1 (HIV-1) Promoter and Induces Tat-Independent HIV-1 Expression but Blunts Cell Activation

Klichko

Archin

Kaur

et al. 2006

J Virol

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Section: Discussionmentioning

confidence: 51%

“…HDAC inhibitors do not alter the expression of activation markers on the surface lymphocytes (78), while prostratin enhances the expression of CD25 and CD69 (5). HMBA, however, down-regulates the activation marker CD25 and the proliferation marker Ki67 in PBMCs.…”

Section: Discussionmentioning

confidence: 99%

Hexamethylbisacetamide Remodels the Human Immunodeficiency Virus Type 1 (HIV-1) Promoter and Induces Tat-Independent HIV-1 Expression but Blunts Cell Activation

Klichko

Archin

Kaur

et al. 2006

J Virol

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“…In cell lines, prostratin can stimulate HIV transcription through NF-kB activation, mediated by PKC [165]. Prostratin has also been shown in other studies to reactivate latent HIV from primary blood lymphocytes and lymphoid tissue and inhibit infection of HIV by down-regulating the expression of the co-receptors CXCR4 and CD4, thus increasing the chance of HIV purging without the risk of new rounds of HIV infection [166][167]. Prostratin, alone, has been shown to reactivate latent HIV from thymocytes and primary human peripheral blood lymphocytes in the SCID-hu (Thy/Liv) model, in the absence of cellular proliferation [168].…”

Section: Induction Of Viral Expressionmentioning

confidence: 96%

Characterisation, Evaluation and Clinical Significance of Latent HIV-1 Reservoirs and Therapeutic Strategies for HIV Eradication

Williams¹,

Fidler²,

Frater³

2011

Recent Translational Research in HIV/AIDS

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“…In acutely infected cells, prostratin is thought to enhance cellular protection possibly due to cytostatic effects (27). In the context of cancer CXCR4 is well-known to induce cancer cell migration and metastasis (24).…”

Section: Discussionmentioning

confidence: 99%

Potential anticancer effect of prostratin through SIK3 inhibition

et al. 2017

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Abstract. Prostratin, a phorbol ester natural plant compound, has been demonstrated to exert an anti-retroviral effect through activation of latent cluster of differentiation (CD)4+T lymphocytes and inhibition of viral entry into the cell through downregulation of chemokine receptor type 4 (CXCR4) expression. However, the potential effect of prostratin on cancer is yet to be defined. As CXCR4 is well known to induce cancer migration, it was hypothesized that prostratin induces an anti-cancer effect through inhibition of CXCR4 expression. The authors previously demonstrated that high stimulating conditions (sub-minimal IL-17, 0.1 ng/ml, synergized with high salt, Δ0.05 M NaCl) promote breast cancer cell proliferation and CXCR4 expression through upregulation of salt-inducible kinase (SIK)-3. The present study demonstrated that prostratin selectively exerted increased cytotoxicity (IC50 of 7 µM) when breast cancer cells were cultured in high stimulating conditions, compared with regular basal culture conditions (IC50 of 35 µM). Furthermore, the cytotoxic potential of prostratin was increased seven-fold in the four breast cancer cell lines (MCF-7, MDA-MB-231, BT-20 and AU-565) compared with the non-malignant MCF10A breast epithelial cell line. This suggested that prostratin specifically targets cancer cells over normal cells. Mechanistic studies revealed that prostratin inhibited CXCR4 expression in breast cancer cells through downregulation of SIK3 expression. Overall, the data suggest that prostratin is a novel drug target for the pro-oncogenic factor SIK3. These studies could form a basis for further research to evaluate the anticancer effect of prostratin in a combinatorial chemotherapeutic regimen. IntroductionChronic inflammation is a well-established hallmark of cancer proliferation (1). The cellular stress caused by inflammation induces release of cytokine and chemokine factors which induce tumor progression and metastasis (2). Several agents have been suggested to induce chronic inflammation (3). Recent evidence from our lab have demonstrated that breast cancer cells cultured under high salt conditions (Δ0.05 M NaCl, 50% above basal culture conditions) were able to upregulate reactive nitrogen species (4,5). Importantly, sodium-MRI studies in breast cancer patients have demonstrated an increased sodium content, of up to 63% above the surrounding soft tissue, in the breast tumors (6,7). These support a notion that high salt exerts an effector role on tumor progression, either working individually or synergistically to enhance an inflammatory tumor microenvironment. Phospho-proteomic based studies from our laboratory have demonstrated that high salt (Δ0.05 M) synergized with sub-minimal stimulation of IL-17 (0.1 ng/ml) induced upregulation of SIK-3, salt inducible kinase-3, a serine-specific protein kinase in breast cancer cells (8). Mechanistic studies have demonstrated that SIK3 played a crucial role in induction of G1/S-phase release of cell cycle, along with enhanced expression of metastasis specific che...

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Dual Role of Prostratin in Inhibition of Infection and Reactivation of Human Immunodeficiency Virus from Latency in Primary Blood Lymphocytes and Lymphoid Tissue

Abstract: To design strategies to purge latent reservoirs of human immunodeficiency virus type 1 (HIV-1), we investigated mechanisms by which a non-tumor-promoting phorbol ester, prostratin, inhibits infection of CD4 ؉ T lymphocytes and at the same time reactivates virus from latency.

Cited by 81 publications

References 50 publications

Hexamethylbisacetamide Remodels the Human Immunodeficiency Virus Type 1 (HIV-1) Promoter and Induces Tat-Independent HIV-1 Expression but Blunts Cell Activation

Hexamethylbisacetamide Remodels the Human Immunodeficiency Virus Type 1 (HIV-1) Promoter and Induces Tat-Independent HIV-1 Expression but Blunts Cell Activation

Characterisation, Evaluation and Clinical Significance of Latent HIV-1 Reservoirs and Therapeutic Strategies for HIV Eradication

Potential anticancer effect of prostratin through SIK3 inhibition

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