Taxanes + Zinc?: New study [1]. The... - Advanced Prostate...

Advanced Prostate Cancer

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Taxanes + Zinc?

pjoshea13 profile image
6 Replies

New study [1].

The taxane chemotherapy drugs get the name from the yew [genus Taxus]. We are perhaps more familiar with Docetaxel [Taxotere] but Paclitaxel [Taxol], from the Pacific yew, was the first.

"Paclitaxel (PTX) is a first-line chemotherapeutic drug for the treatment of prostate cancer.{?} However, most patients develop resistance and metastasis, and thus new therapeutic approaches are urgently required."

In a cell study - adding zinc [Zn] to Paclitaxel [PTX]:

"Zn and PTX increased proliferation inhibition in a dose- and time-dependent manner in prostate cancer cells, while Zn increased prostate cancer cell chemosensitivity to PTX."

"Our results demonstrated that Zn and PTX combined therapy inhibits EMT {epithelial-mesenchymal transition} by reducing the expression of TWIST1, which reduces the invasion and migration of prostate cancer cells."

"Therefore, Zn may be a potential adjuvant of PTX in treating prostate cancer and combined treatment may offer a promising therapeutic strategy for prostate cancer."

Worth a try if on one of the taxanes. I don't see a downside to the use of zinc.

-Patrick

ncbi.nlm.nih.gov/pubmed/307...

Prostate. 2019 Feb 3. doi: 10.1002/pros.23772. [Epub ahead of print]

Zinc promotes prostate cancer cell chemosensitivity to paclitaxel by inhibiting epithelial-mesenchymal transition and inducing apoptosis.

Xue YN1, Yu BB1, Liu YN1, Guo R1, Li JL1, Zhang LC1, Su J1, Sun LK1, Li Y1.

Author information

1

Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Center, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China.

Abstract

BACKGROUND:

Paclitaxel (PTX) is a first-line chemotherapeutic drug for the treatment of prostate cancer. However, most patients develop resistance and metastasis, and thus new therapeutic approaches are urgently required. Recent studies have identified widespread anti-tumor effects of zinc (Zn) in various tumor cell lines, especially prostate cancer cells. In this study, we examined the effects of Zn as an adjuvant to PTX in prostate cancer cells.

METHODS:

PC3 and DU145 cells were treated with different concentrations of Zn and/or PTX. MTT assay was used to detect cell viability. Real-time cell analysis (RTCA) and microscopy were used to observe morphological changes in cells. Western blotting was used to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins. qPCR (reverse transcription-polymerase chain reaction) was used to examine changes in TWIST1 mRNA levels. Cell invasion and migration were detected by scratch and transwell assays. shRNA against TWIST1 was used to knockdown TWIST1. Colony formation assay was used to detect cell proliferation, while Annexin V and propidium iodide (PI) staining was used to detect cell apoptosis.

RESULTS:

Zn and PTX increased proliferation inhibition in a dose- and time-dependent manner in prostate cancer cells, while Zn increased prostate cancer cell chemosensitivity to PTX. Combined Zn and PTX inhibited prostate cancer cell invasion and migration by downregulating the expression of TWIST1. Furthermore, knockdown of TWIST1 increased the sensitivity of prostate cancer cells to PTX. In addition, Zn and PTX reduced cell proliferation and induced apoptosis in prostate cancer cells.

CONCLUSIONS:

Our results demonstrated that Zn and PTX combined therapy inhibits EMT by reducing the expression of TWIST1, which reduces the invasion and migration of prostate cancer cells. SiTWIST1 increased the sensitivity of prostate cancer cells to PTX. In addition, with prolonged treatment, Zn and PTX inhibited proliferation and led to prostate cancer cell apoptosis. Therefore, Zn may be a potential adjuvant of PTX in treating prostate cancer and combined treatment may offer a promising therapeutic strategy for prostate cancer.

© 2019 Wiley Periodicals, Inc.

KEYWORDS:

EMT; TWIST1; invasion; migration

PMID: 30714183 DOI: 10.1002/pros.23772

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6 Replies
NPfisherman profile image
NPfisherman

Have you seen any studies with Zn and Docetaxol, or are there any pending? One might assume that Zn would also be synergistic in treatment with Docetaxol, but one can not assume anything....especially when it comes to prostate cancer...

As always, thank you for posting...

pjoshea13 profile image
pjoshea13 in reply toNPfisherman

Yes, one should not assume that zinc would work well with all taxanes, but I would continue to take my 50 mg zinc citrate every day.

-Patrick

ITCandy profile image
ITCandy

This article regarding zinc supplementation concerns me.

jamanetwork.com/journals/ja...

Is it possible for zinc to accumulate in the body while supplementing 50mg daily as well as getting it from food sources. I take 50mg zinc citrate daily as well but just want to ensure that I'm fighting my pca and not feeding it.

pjoshea13 profile image
pjoshea13 in reply toITCandy

I posted something on this 3 years ago in: "Zinc - Clioquinol":

healthunlocked.com/advanced...

Read from:

"Some may have heard that zinc can actually promote PCa."

-Patrick

Kuanyin profile image
Kuanyin

Choose your study.

Prostate. 2017 May;77(6):604-616. doi: 10.1002/pros.23304. Epub 2017 Jan 19.

Amino Acid Profiling of Zinc Resistant Prostate Cancer Cell Lines: Associations With Cancer Progression.

Kratochvilova M1,2, Raudenska M1,2, Heger Z2,3, Richtera L2,3, Cernei N2,3, Adam V2,3, Babula P1, Novakova M1, Masarik M1,2,4, Gumulec J1,4.

Author information

Abstract

BACKGROUND:

Failure in intracellular zinc accumulation is a key process in prostate carcinogenesis. Nevertheless, epidemiological studies of zinc administration have provided contradicting results. In order to examine the impact of the artificial intracellular increase of zinc(II) ions on prostate cancer metabolism, PNT1A, 22Rv1, and PC-3 prostatic cell lines-depicting different stages of cancer progression-and their zinc-resistant counterparts were used. To determine "benign" and "malignant" metabolic profiles, amino acid patterns, gene expression, and antioxidant capacity of these cell lines were assessed.

METHODS:

Amino acid profiles were examined using an ion-exchange liquid chromatography. Intracellular zinc content was measured by atomic absorption spectrometry. Metallothionein was quantified using differential pulse voltammetry. The content of reduced glutathione was determined using high performance liquid chromatography coupled with an electrochemical detector. Cellular antioxidant capacity was determined by the ABTS test and gene expression analysis was performed by qRT-PCR.

RESULTS AND CONCLUSIONS:

Long-term zinc treatment was shown to reroute cell metabolism from benign to more malignant type. Long-term application of high concentration of zinc(II) significantly enhanced cisplatin resistance, invasiveness, cellular antioxidant capacity, synthesis of glutathione, and expression of treatment resistance- and stemness-associated genes (SOX2, POU5F1, BIRC5). Tumorous cell lines universally displayed high accumulation of aspartate and sarcosine and depletion of essential amino acids. Increased

I think for the time being I will pass on zinc and get whatever my body requires through fruits and vegetables.

podsart profile image
podsart

Patrick

Your energy and ability to continually provide us with relevant clinical info is amazing and much appreciated.

Thank you

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