Prostate cancer treatment enhanced by ultrasound.
October 12, 2005
Subject: Ultrasound treatment of prostate cancer increases effectiveness of quercetin.
It is well established that prostate cancer cells are sensitive to quercetin, a plant chemical found in onions, apples, wine and other plants. Although the exact mechanisms of action aren't yet known, it is well accepted that quercetin slows down prostate cancer cell growth or stimulates their self destruction through apoptosis. [i]
It is also pretty well accepted that for some reason prostate cancer cells are sensitive to heat. Warming them up kills them. [ii] There are various Ďalternative cancer therapy' gadgets that attempt to deliver heat to the prostate gland.
It seems you can put these two bits of information together. Quercetin treatment of prostate cancer cells increases their sensitivity to heat.(or perhaps its the other way around, bottom line is for a prostate cancer cell quercetin and heat don't mix)[iii]
One of the easiest ways to deliver heat into specific areas of the body is through the use of therapeutic ultrasound machines. These aren't the gadgets that they look inside the body with, like to see what sex the baby is. These ultrasound machines simply project ultrasound vibrations into the tissue. The vibration is converted to heat. You'll see these gadgets in physical therapy settings. They can warm up the tissue deep below the skin.
Quercetin pretreatment followed by ultrasound treatment may become a simple and effective adjunct treatment for prostate cancer. In a study published in the British Journal of Cancer in February, 2005, three researcher from the University of California in Santa Barbara reported on their experiments. They found that a short application of ultrasound selectively sensitizes prostate cancer cells to quercetin. Non cancerous cells were unaffected. Ultrasound treatment increased the toxic effect of quercetin on cancer cells by 8,000%. [iv]
If you didn't say wow when you read that, go back and reread it. These guys reported a similar effect on skin cancer cells. Again the effect is selective, killing cancerous cells and leaving healthy ones alone.
Professional ultrasound machines cost between two to three thousand dollars. There are small cheap machines designed for home use in the $100-200 range.
Ultrasound treatments should be added to our growing list of alternative prostate cancer therapies. They should also be considered in prevention programs for both prostate and skin cancer.
Ultrasound machines for sale:
cheap ultrasound machine $240
or even cheaper:
more expensive professional machine $2200
[i] J Cancer Res Clin Oncol. 2005 Jul 28;:1-7 [Epub ahead of print]
Quercetin-induced growth inhibition and cell death in prostatic carcinoma cells (PC-3) are associated with increase in p21 and hypophosphorylated retinoblastoma proteins expression.
Vijayababu MR, Kanagaraj P, Arunkumar A, Ilangovan R, Aruldhas MM, Arunakaran J.
Department of Endocrinology, Dr. ALM Postgraduate Institute of Basic Medical Sciences, University of Madras , Taramani campus, Chennai, 600 113, India , firstname.lastname@example.org.
Prostate cancer is the major health problem and the leading cause of male cancer death. Quercetin is a novel antitumor and antioxidant, whose molecular mechanism involved in cell cycle arrest in androgen independent prostate cancer cells remains unclear. In this study, we investigated the effects of quercetin on proliferation and cell cycle arrest by modulation of Cdc2/Cdk-1 protein in prostate cancer cells (PC-3). PC- 3 cells are human androgen independent cancer cells and were cultured with quercetin at concentrations of 50 and 100 muM for 24 h. Cell proliferation, apoptosis and cell cycle distribution were analyzed. Expression of Cdc2/Cdk-1, cyclin B1, cyclin A, p21/Cip1, pRb, pRb2/p130, Bcl-2, Bcl-X(L), Bax and caspase-3 proteins were studied with western blot analysis. Addition of quercetin led to substantial decrease in the expression of Cdc2/Cdk-1, cyclin B1 and phosphorlyated pRb and increase in p21. Flowcytometric analysis showed that quercetin blocks G2-M transition, with significant induction of apoptosis. Apoptosis markers like Bcl-2 and Bcl-X(L) were significantly decreased and Bax and caspase-3 were increased. From this study, it was concluded that quercetin inhibits prostate cancer cell proliferation by altering the expression of cell cycle regulators and apoptotic proteins.
PMID: 16049707 [PubMed - as supplied by publisher]
[ii] Prostate. 2004 Feb 1;58(2):109-20.
Response to sublethal heat treatment of prostatic tumor cells and of prostatic tumor infiltrating T-cells.
Kramer G, Steiner GE, Grobl M, Hrachowitz K, Reithmayr F, Paucz L, Newman M, Madersbacher S, Gruber D, Susani M, Marberger M.
Department of Urology, University of Vienna , Austria .
BACKGROUND: To investigate the possibilities offered by high intensity focused ultrasound (HIFU) in the field of tumor vaccination, we analyzed how prostatic cancer (CaP) cells react towards heat treatment and whether increased access to CaP cells by the immune system would be the result. METHODS: Heat/stress response of CaP cells in situ and of CaP cell lines was analyzed by immunohistochemistry, Western blotting, and Atlas array. A heat-induced change in immune recognition was analyzed functionally using human T-helper (Th)1 and Th2-cytokine release with tumor infiltrating T-lymphocytes (TIL) as responder and autologous CaP cells either heated or untreated as stimulator cells. RESULTS: Transcription of 68 out of 500 genes was upregulated by sublethal heat in LNCaP and PC3 cells. Significantly upregulated stress protein (SP) expression (HSP-72, -73, GRP-75, -78) was seen at the border zone of HIFU treatment. Remarkably, even untreated benign prostatic hyperplasia (BPH) specimens revealed relative overexpression of heat shock protein (HSP)-72, -73 and glucose regulated protein (GRP)-75, -78. Heated CaP cells increased Th1-cytokine (IL-2, IFN-gamma, TNF-alpha) release but decreased Th2-cytokine (IL-4, -5, -10) release of TIL. CONCLUSIONS: HIFU treatment may alter the presentation of prostate tissue and tumor antigens and this presentation is most likely stimulatory. HSP-72/73 overexpression in untreated BPH may suggest a mechanism by which BPH can incite inflammation. Copyright 2003 Wiley-Liss, Inc.
[iii] Int J Urol. 2001 Nov;8(11):623-30.
Effects of quercetin on the heat-induced cytotoxicity of prostate cancer cells.
Nakanoma T, Ueno M, Iida M, Hirata R, Deguchi N.
Department of Urology, Saitama Medical School , Saitama , Japan . email@example.com
BACKGROUND: It has been demonstrated that prostate cancer cells are relatively sensitive to heat stress. We have reported that heat treatment at 43 degrees C increases the expression of heat shock protein 70 (hsp70) in prostate cancer cells, leading to apoptosis. Hsp70 is a protein that protects cells against heat damage. Cells with lower levels of hsp70 have been shown to have a higher sensitivity to heat stress. Therefore, downregulation of hsp70 is expected to enhance heat-induced inhibitory effects on cell growth. Quercetin has been reported to be an agent that inhibits hsp70 expression. The present study was undertaken to investigate the effects of quercetin and/or heat on the growth of prostate cancer cells in vitro. METHODS: Three human prostate cancer cell lines were used: Lncap; PC-3; and JCA-1. The cells were treated with quercetin and/or heat. Alterations in the cell cycle and hsp70 expression were examined by means of flow cytometry (FCM). The apoptotic cells were detected by FCM using fluorescein isothiocyanate (FITC) labeled annexin V. RESULTS: Treatment with quercetin alone resulted in an apparent decrease of hsp70-positive cells and an increase of subG1 cells in JCA-1 and LNcap cells. Quercetin inhibited an increase of hsp70 expression after heat treatment and increased the number of subG1 cells with lower levels of hsp70 in JCA-1 and LNcap cells. Quercetin was found to enhance heat-induced inhibitory effects on cell growth and heat-induced apoptosis in both JCA-1 and LNcap cells. CONCLUSION: These results suggest that quercetin may enhance heat-induced cytotoxicity in prostate cancer cell lines through the inhibition of hsp70 production.
[iv] Br J Cancer. 2005 Feb 14;92(3):499-502.
Induction of cancer-specific cytotoxicity towards human prostate and skin cells using quercetin and ultrasound.
Paliwal S, Sundaram J, Mitragotri S.
Department of Chemical Engineering, University of California , Santa Barbara , CA 93106-5080 , USA .
Bioflavonoids, such as quercetin, have recently emerged as a new class of chemotherapeutic drugs for the treatment of various cancer types, but are marred by their low potency and poor selectivity. We report that a short application of low-frequency ultrasound selectively sensitises prostate and skin cancer cells against quercetin. Pretreatment of cells with ultrasound (20 kHz, 2 W cm(-2), 60 s) selectively induced cytotoxicity in skin and prostate cancer cells, while having minimal effect on corresponding normal cell lines. About 90% of the viable skin cancer cell population was lost within 48 h after ultrasound-quercetin (50 microM) treatment. Ultrasound reduced the LC50 of quercetin for skin cancer cells by almost 80-fold, while showing no effect on LC50 for nonmalignant skin cells.
PMID: 15685239 [PubMed - indexed for MEDLINE]