Alpha-tomatine attenuation of in vivo growth of subcutaneous and orthotopic xenograft tumors of human prostate carcinoma PC-3 cells is accompanied by inactivation of nuclear factor-kappa B signaling
Authors: John David Hooper
Pooi-Fong Wong
Hui He
Sui-Ting Lee
Mohd Rais Mustafa
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: NF-κB; α-tomatine; prostate cancer; apoptosis; IκBα kinase
Affiliations: Department of Pharmacology, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia.

Abstract:  Background: Nuclear factor-kappa B (NF-κB) plays a role in prostate cancer and agents that suppress its activation may inhibit development or progression of this malignancy. Alpha (α)-tomatine is the major saponin present in tomato (Lycopersicon esculentum) and we have previously reported that it suppresses tumor necrosis factor-alpha (TNF-α)-induced nuclear translocation of nuclear factor-kappa B (NF-κB) in androgen-independent prostate cancer PC-3 cells and also potently induces apoptosis of these cells. However, the precise mechanism by which α-tomatine suppresses NF-κB nuclear translocation is yet to be elucidated and the anti-tumor activity of this agent in vivo has not been examined. Methodology/principal findings: In the present study we show that suppression of NF-κB activation by α-tomatine occurs through inhibition of I kappa B alpha (IκBα) kinase activity, leading to sequential suppression of IκBα phosphorylation, IκBα degradation, NF-κB/p65 phosphorylation, and NF-κB p50/p65 nuclear translocation. Consistent with its ability to induce apoptosis, α-tomatine reduced TNF-α induced activation of the pro-survival mediator Akt and its inhibition of NF-κB activation was accompanied by significant reduction in the expression of NF-κB-dependent anti-apoptotic (c-IAP1, c-IAP2, Bcl-2, Bcl-xL, XIAP and survivin) proteins. We also evaluated the antitumor activity of α-tomatine against PC-3 cell tumors grown subcutaneously and orthotopically in mice. Our data indicate that intraperitoneal administration of α-tomatine significantly attenuates the growth of PC-3 cell tumors grown at both sites. Analysis of tumor material indicates that the tumor suppressing effects of α-tomatine were accompanied by increased apoptosis and lower proliferation of tumor cells as well as reduced nuclear translocation of the p50 and p65 components of NF-κB. Conclusion/significance: Our study provides first evidence for in vivo antitumor efficacy of α-tomatine against the human androgen-independent prostate cancer. The potential usefulness of α-tomatine in prostate cancer prevention and therapy requires further investigation. 

Retracted: No

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 Just checking in with the authors; it has been a while since we discussed this. There is still no correction. Could you please check? , 
 It took the journal almost eight years to issue the correction, on May 3, 2022: https: journals.plos.org plosone article?id=10.1371 journal.pone.0268234  *During the preparation of Fig 2 the incorrect IKKu03b2 data were used inadvertently, so that the Fig 2C TNF-u03b1 + tomatine IKKu03b2 panel and the Fig 2D IKKu03b2 panel are incorrect. The correct panels have been included in the updated version of Fig 2 provided with this notice.* *The available data underlying the Fig 2C and 2D panels are provided in the S1 File below. The original data underlying Fig 2A, 2B and 2E, and Fig 5 are no longer available due to the time elapsed since the experiments took place.* *The authors provided updated [1] versions of Figs 2 and 5 in a public comment posted on this article in 2014, and they submitted the underlying data presented in the S1 File and updated figures for this article for editorial review by PLOS in 2015. The PLOS ONE Editors sincerely regret that this case was not resolved much sooner after the prior correspondence.* ,