Knowing artemisinin can put dogs with bone cancer into remission, I was wondering if it could also help with bone metastases, so I did a search and came up with this fecent report - just out last week. Can anyone here who can traslate this tell if this may be another very promising new treatment? TIA!
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Sunday, January 7, 2018
Targeting NF-kappa B Signaling by Artesunate Restores Sensitivity of Castrate-Resistant Prostate Cancer Cells to Antiandrogens.
Targeting NF-kappa B Signaling by Artesunate Restores Sensitivity of Castrate-Resistant Prostate Cancer Cells to Antiandrogens.
Neoplasia. 2017; 19(4):333-345 (ISSN: 1476-5586)
Nunes JJ; Pandey SK; Yadav A; Goel S; Ateeq B
Androgen deprivation therapy (ADT) is the most preferred treatment for men with metastatic prostate cancer (PCa). However, the disease eventually progresses and develops resistance to ADT in majority of the patients, leading to the emergence of metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed artesunate (AS), an artemisinin derivative, for its anticancer properties and ability to alleviate resistance to androgen receptor (AR) antagonists. We have shown AS in combination with bicalutamide (Bic) attenuates the oncogenic properties of the castrate-resistant (PC3, 22RV1) and androgen-responsive (LNCaP) PCa cells. Mechanistically, AS and Bic combination inhibits nuclear factor (NF)-κB signaling and decreases AR and/or AR-variant 7 expression via ubiquitin-mediated proteasomal degradation. The combination induces oxidative stress and apoptosis via survivin downregulation and caspase-3 activation, resulting in poly-ADP-ribose polymerase (PARP) cleavage. Moreover, preclinical castrate-resistant PC3 xenograft studies in NOD/SCID mice (n =28, seven per group) show remarkable tumor regression and significant reduction in lungs and bone metastases upon administering AS (50 mg/kg per day in two divided doses) and Bic (50 mg/kg per day) via oral gavage. Taken together, we for the first time provide a compelling preclinical rationale that AS could disrupt AR antagonist-mediated resistance observed in mCRPC. The current study also indicates that the therapeutic combination of Food and Drug Administration-approved AS or NF-κB inhibitors and AR antagonists may enhance the clinical efficacy in the treatment of mCRPC patients.
Major Subject Heading(s) Minor Subject Heading(s) CAS Registry / EC Numbers
"Conclusion Long-term treatment with A. annua capsules combined with short-term bicalitumide treatment resulted in considerable regression of advanced metastasized prostate carcinoma. "
Artemisia annua L, artemisinin and artesunate reveal profound activity not only against malaria, but also against cancer in vivo and clinical trials. Longitudinal observations on the efficacy of A. annua in patients are, however missing as of yet.
Methods
Clinical diagnosis was performed by imaging techniques (MRT, scintigraphy, SPECT/CT) and blood examinations of standard parameters from clinical chemistry. Immunohistochemistry of formalin-fixed, paraffin-embedded tumor material was performed to determine the expression of several biomarkers (cycloxygenase-2 (COX2), epidermal growth factor receptor (EGFR), glutathione S-transferase P1 (GSTP1), Ki-67, MYC, oxidized low density lipoprotein (lectin-like) receptor 1 (LOX1), p53, P-glycoprotein, transferrin receptor (TFR, CD71), vascular endothelial growth factor (VEGF), von Willebrand factor (CD31)). The immunohistochemical expression has been compared with the microarray-based mRNA expression of these markers in two prostate carcinoma cell lines (PC-3, DU-145).
Results
A patient with prostate carcinoma (pT3bN1M1, Gleason score 8 (4+4)) presented with a prostate specific antigen (PSA) level >800 µg/l. After short-term treatment with bacalitumide (50 mg/d for 14 days) and long-term oral treatment with A. annua capsules (continuously 5 × 50 mg/d), the PSA level dropped down to 0.98 µg/l. MRT, scintigraphy and SPECT/CT verified tumor remission. Seven months later, PSA and ostase levels increased, indicating tumor recurrence and skeletal metastases. Substituting A. annua capsules by artesunate injections (2 × 150 mg twice weekly i.v.) did not prohibit tumor recurrence. PSA and ostase levels rose to 1245 µg/l and 434 U/l, respectively, and MRT revealed progressive skeletal metastases, indicating that the tumor acquired resistance. The high expression of MYC, TFR, and VEGFC in the patient biopsy corresponded with high expression of these markers in the artemisinin-sensitive PC-3 cells compared to artemisinin-resistant DU-145 cells.
Conclusion
Long-term treatment with A. annua capsules combined with short-term bicalitumide treatment resulted in considerable regression of advanced metastasized prostate carcinoma. Controlled clinical trials are required to evaluate the clinical benefit of A. annua in prostate cancer.
Note: Artesunate is a prodrug that is rapidly converted to its active form dihydroartemisinin.
The idea is that it gets into cells based on how much iron there is. Cancer often accumulates iron. Without the iron, a killing dose will not be taken up.
I tried otc artemisinin years ago. I was also taking IP6 which chelates iron. Stupid mistake. So it didn't work for me.
This is something that should be tried only on a short-term basis. Can be repeated, but should not be used chronically.
"AS and Bic combination inhibits nuclear factor (NF)-κB signaling"
Many of the polyphenols we take are NF-κB inhibitors. We don't need artemisinin for that.
Interesting as a medical professional friend of mine just recommended the IP6. What about taking the artemisinin alone, nothing else outside of the meds for prostate cancer. I'm reading so much encouraging research about the use of artemisinin for prostate cancer. I believe you need to take it on/off - ie, one week on, one week off.
I am just beginning to research this stuff as I am frantically trying to educate myself after my husband recently (2 weeks ago) learned he has become CRPC less than 11 months after being diagnosed with the St4 PC. This happened after what he thought was 'just' sciatica turned out to be tumor activity on his lower spine - via an MRI. Horrible news, as we were expecting the hormone treatment to work for at least a couple years. For this he started radiation treatment and today just had his 4th of 10 consecutive treatments. He got terribly sick after his 2nd treatment (severe nausea). Yesterday his oncologist told him to stop the Casodex His last Lupron shot was December 10th, about a month ago, so at least he still has that in his system. I worry because the oncologist doesn't want him to do anything else until after he finished radiation. He suggested one of the Clinical trials at U of C using Zytiga + Oliparib, but I just read some of the possible permanent side effects of Oliparib - scary!! So maybe he should just go on Zytiga alone. This is all so VERY scary!! -and my husband doesn't want to do any research - so it's just me, pus listening to the oncologist - a prostate cancer specialist who poo poos supplements and special diets. fwiw, his PSA yesterday was at 1.33.
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I would like to connect with fellow warriors that are HSPC and on Darolutamide to discuss Time to Failure, early detection assays etc...
Clarity Update: Complete response in first patient ever treated with 2 doses of Cu-67 SAR-bisPSMA at 8GBq
'Substandard' Control Arms in Clinical Trials– Practice found common in prostate cancer studies
Masofaniten +Enzalutamide This could be a game changer...Science is coming to our aid
