Gold(III)-Dithiocarbamato Peptidomimetics in the Forefront of the Targeted Anticancer Therapy: Preclinical Studies against Human Breast Neoplasia

Since the serendipitous discovery of cisplatin, platinum-based drugs have become well-established antitumor agents, despite the fact that their clinical use is limited by many severe side-effects. In order to both improve the chemotherapeutic index and broaden the therapeutic spectrum of current drugs, our most recent anti-neoplastic agents, Au(III) complexes, were designed as carrier-mediated delivery systems exploiting peptide transporters, which are up-regulated in some cancers. Among all, we focused on two compounds and tested them on human MDA-MB-231 (resistant to cisplatin) breast cancer cell cultures and xenografts, discovering the proteasome as a major target both in vitro and in vivo. 53% inhibition of breast tumor growth in mice was observed after 27 days of treatment at 1.0 mg kgSUP−1 dSUP−1, compared to control. Remarkably, if only the most responsive mice are taken into account, 85% growth inhibition, with some animals showing tumor shrinkage, was observed after 13 days. These results led us to file an international patent, recognizing this class of gold(III) peptidomimetics as suitable candidates for entering phase I clinical trials

Editorial: Unravelling Copper-Regulatory Systems and Copper-Affected Pathways in Cancer Cells to Improve Current Therapies

Unravelling Copper-Regulatory Systems and Copper-Affected Pathways in Cancer Cells to Improve Current Therapie

Methods for preventing and treating cancer using N-thiolated β-lactam compounds and analogs thereof

The subject invention concerns N-thiolated β-lactam compounds of formula A, wherein R1 is a hydrocarbon group having 1–8 carbon atoms; R3 is an organothio group; and R4 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, cycloalkenyl, or heterocycloalkenyl, and analogs and pharmaceutically acceptable salts, esters and amides thereof. The subject invention also concerns methods for inducing tumor cell death or inhibiting tumor cell proliferation, and methods for inducing DNA damage, inhibiting DNA replication, activating p38 MAP kinase, or activating caspase cascade activation, or releasing cytochrome C from mitochondria into the cytoplasm in a tumor cell. Methods for treating cancer using N-thiolated β-lactam compounds, as well as pharmaceutical compositions comprising the same are further disclosed

Polyphenol proteasome inhibitors, synthesis, and methods of use

The present invention relates to synthetic green tea derived polyphenolic compounds, their modes of syntheses, and their use in inhibiting proteasomal activity and in treating cancers. The present invention is also directed to pharmaceutical compositions useful in methods of inhibiting proteasomes and of treating cancers

Activation of AMP-Activated Protein Kinase by 3,39-Diindolylmethane (DIM) Is Associated with Human Prostate Cancer Cell Death \u3cem\u3eIn Vitro\u3c/em\u3e and \u3cem\u3eIn Vivo\u3c/em\u3e

There is a large body of scientific evidence suggesting that 3,39-Diindolylmethane (DIM), a compound derived from the digestion of indole-3-carbinol, which is abundant in cruciferous vegetables, harbors anti-tumor activity in vitro and in vivo. Accumulating evidence suggests that AMP-activated protein kinase (AMPK) plays an essential role in cellular energy homeostasis and tumor development and that targeting AMPK may be a promising therapeutic option for cancer treatment in the clinic. We previously reported that a formulated DIM (BR-DIM; hereafter referred as B-DIM) with higher bioavailability was able to induce apoptosis and inhibit cell growth, angiogenesis, and invasion of prostate cancer cells. However, the precise molecular mechanism(s) for the anti-cancer effects of B-DIM have not been fully elucidated. In the present study, we investigated whether AMP-activated protein kinase (AMPK) is a molecular target of B-DIM in human prostate cancer cells. Our results showed, for the first time, that B-DIM could activate the AMPK signaling pathway, associated with suppression of the mammalian target of rapamycin (mTOR), down-regulation of androgen receptor (AR) expression, and induction of apoptosis in both androgen-sensitive LNCaP and androgen-insensitive C4-2B prostate cancer cells. B-DIM also activates AMPK and down-regulates AR in androgen-independent C4-2B prostate tumor xenografts in SCID mice. These results suggest that B-DIM could be used as a potential anti-cancer agent in the clinic for prevention and/or treatment of prostate cancer regardless of androgen responsiveness, although functional AR may be required

Observation of ηc→ωω\eta_c\to\omega\omega in J/ψ→γωωJ/\psi\to\gamma\omega\omega

Using a sample of $(1310.6\pm7.0)\times10^6$ $J/\psi$ events recorded with the BESIII detector at the symmetric electron positron collider BEPCII, we report the observation of the decay of the $(1^1 S_0)$ charmonium state $\eta_c$ into a pair of $\omega$ mesons in the process $J/\psi\to\gamma\omega\omega$. The branching fraction is measured for the first time to be $\mathcal{B}(\eta_c\to\omega\omega)= (2.88\pm0.10\pm0.46\pm0.68)\times10^{-3}$, where the first uncertainty is statistical, the second systematic and the third is from the uncertainty of $\mathcal{B}(J/\psi\to\gamma\eta_c)$. The mass and width of the $\eta_c$ are determined as $M=(2985.9\pm0.7\pm2.1)\,$MeV/$c^2$ and $\Gamma=(33.8\pm1.6\pm4.1)\,$MeV.Comment: 13 pages, 6 figure

Observation of e+e−→ωχc1,2e^+e^- \rightarrow \omega \chi_{c1,2} near s\sqrt{s} = 4.42 and 4.6 GeV

Based on data samples collected with the BESIII detector operating at the BEPCII storage ring at center-of-mass energies $\sqrt{s} >$ 4.4 GeV, the processes $e^+e^- \rightarrow \omega \chi_{c1,2}$ are observed for the first time. With an integrated luminosity of $1074 pb^{-1}$ near $\sqrt{s} =$ 4.42 GeV, a significant $\omega \chi_{c2}$ signal is found, and the cross section is measured to be (20.9 \pm 3.2 \pm 2.5)\pb. With $567 pb^{-1}$ near $\sqrt{s} =$ 4.6 GeV, a clear $\omega \chi_{c1}$ signal is seen, and the cross section is measured to be (9.5 \pm 2.1 \pm 1.3) \pb, while evidence is found for an $\omega \chi_{c2}$ signal. The first errors are statistical and the second are systematic. Due to low luminosity or low cross section at other energies, no significant signals are observed. In the $\omega \chi_{c2}$ cross section, an enhancement is seen around $\sqrt{s} =$ 4.42 GeV. Fitting the cross section with a coherent sum of the $\psi(4415)$ Breit-Wigner function and a phase space term, the branching fraction $\mathcal{B}(\psi(4415)\to\omega\chi_{c2})$ is obtained to be of the order of $10^{-3}$.Comment: 7 pages, 3 figure

Fujiki

ABSTRACT Prostate cancer cells demonstrate slow growth kinetics and chemoresistance. Tea polyphenols have been shown to exert prostate cancer-preventative effects. Here we report that growth-arrested prostate cancer cells expressed high levels of a hyperphosphorylated Bcl-X L in mitochondria. Treatment with tea polyphenols or the major tea component epigallocatechin-3-gallate blocked expression of the hyper-, but not hypophosphorylated Bcl-X L in mitochondria, accompanied by cytochrome c release, caspase activation, and apoptosis. Studies using specific inhibitors suggest that tea inhibits p38 mitogenactivated protein kinase and the proteasome activities, leading to inhibition of Bcl-X L phosphorylation and induction of prostate cancer cell death. Epidemiological and animal studies have demonstrated the cancer preventative properties of green tea polyphenols (GTP) (Liao et a