Sound Waves Kill Skin and Prostate Cancer Cells

Anonymous Coward writes "A recent Study in the British Journal of Cancer shows that the use of Quercitin and 20KHz ultrasound for 60 seconds killed skin and prostate cancer cells. 90% of the abnormal cells were dead within 48hrs. Since low frequency ultrasound was previously shown to enhance the skin penetration of topical substances up to 1000 times, it would seem that a topical Quercetin cream with a low frequency ultrasound wand might be just the ticket for those annoying little skin cancers that tend to occur in older geeks who have spent a bit of time in the sun."

Text of Article for those who can't get BJC

[Anonymous Coward]

Therapeutic selectivity plays a crucial role in determining the success of chemotherapy. Some of the current targeted therapies attempt to localise drugs to cancer cells based on overexpression of epidermal growth factor receptors (EGFR) (Mendelsohn and Baselga, 2000) or angiogenesis (Carter, 2001). Antibodies, inhibitors, antisense therapy and gene therapy are also among a few strategies that have gained momentum (Guillemard and Saragovi, 2004). Many of these strategies have now reached clinical trials; however, these methods are still limited by issues including low potency, delivery complications, multi-drug resistance, side effects, collateral damage (Tattersall and Clarke, 2003) or incomplete success (Lynch et al, 2004). In an attempt to develop a targeted chemotherapeutic strategy, we propose the use of bioflavonoids, which are common dietary supplements, in conjunction with low-frequency ultrasound. Quercetin, a major bioflavonoid in human diet, has been identified as a chemotherapeutic agent for the treatment of breast cancer (Singhal et al, 1995; Choi et al, 2001), colon cancer (Salucci et al, 2002), ovarian cancer (Chan et al, 2003) and prostate cancer (Knowles et al, 2000; Nakanoma et al, 2001; Kobayashi et al, 2002). Antiproliferative action of quercetin is hypothesised to be mediated by attenuating phosphorylation of activated hsp transcription factor (hsf), shortly after its trimerisation (Nagai et al, 1995; Lee et al, 1998), thereby resulting in increased susceptibility of hsf to proteolytic degradation and as a consequence inhibiting all downstream events, including hsp expression (Li et al, 1999). Since hsps are constitutively overexpressed in many tumours (Jaattela, 1999), inhibition of hsps is an attractive chemotherapeutic strategy. hsps form a complex with mutant p53 protein (mp53), thereby prolonging the half-life of malignant mp53 and allowing tumour cells to bypass the normal mechanism of cell cycle arrest (Selkirk et al, 1996). In spite of its therapeutic benefits, utilisation of quercetin in clinical applications has been limited by low potency and poor specificity. Additionally, it is difficult to sustain therapeutic quercetin concentrations in blood by oral ingestion (Lamson and Bringall, 2000). Here, through in vitro studies, we demonstrate for the first time, using two pairs of normal and cancer cells (human skin fibroblast and human prostate epithelial cells), that ultrasound selectively sensitises cancer cells against quercetin. LC50 of quercetin for skin cancer cells is selectively decreased by almost 80-fold by a short pretreatment with ultrasound. MATERIALS AND METHODS Cell culture Normal and cancer cells derived from prostrate and skin tissues were investigated in this study. DU145 prostate cancer cells were provided by Dr L Wilson at UC Santa Barbara, CA, USA. Nonmalignant prostrate normal cells (Catalog No. CRL-11609), nonmalignant skin cells (Catalog No. CRL-7761) and skin cancer cells (Catalog No. CRL-7762) were obtained from the American Type Culture Collection (ATCC, Rockville, MD, USA). All cells were grown as monolayers and were kept in a 5% CO2 environment at 371C. Cell cultures were maintained in Dulbecco's modified Eagle's medium (DMEM) with glucose (1 g l1), NaHCO3 (3.7 g l1), L-glutamine (2mM), nonessential amino acids (0.0815 g l1) and 10% FBS. Antibiotic-antimycotic cocktail (Catalog No. 15240-062, Gibco, Invitrogen Corporation, Carlsbad, CA, USA), at a final concentration of 100Uml1 of penicillin, 100 mgml1 of streptomycin and 0.25 mgml1 of amphotericin B, was added to all cultures. Cells were harvested at a concentration of about 3105 cells ml1, by washing with versene (NaCl - 8 g l1, KCl - 0.2 g l1, NaH2PO4 - 1.15 g l1, K2HPO4 - 0.2 g l1, Na2- EDTA - 0.2 g l1 in distilled water with pH adjusted to 7.2) followed by 2-3-min digestion with trypsin/EDTA (0.25%/0.02%). Revised 1 November 2004; accepted 18 November 2004; published online 1 February 2005 *Correspondence: Dr S Mitragotri; E-mail: [e-mail] Ultrasound application and quercetin treatment Aliquo

Re:Slight problem eh?

[Anonymous Coward]

well they do use liquid nitrogen to freeze off skin tumors but Nitrogen condenses at a balmy 77 K.
And since when is 20 kHz 'low frequency'

Re:Misleading headline

[Anonymous Coward]

It sensitizes the cells as well as acting as a penetrant for
the Quercetin. BTW calling Quercetin a drug is a misnomer. It
is a nutrient (bioflavanoid to be specific).

Re:Slight problem eh?

[Anonymous Coward]

"And since when is 20 kHz 'low frequency'"

Sorry, there wasn't enough room to put Low Frequency Ultrasound
in the title. 20KHz is considered the low end of ultrasound.
Happy?

Re:Slight problem eh?

[qbwiz]

KHz is Kelvin-Hertz. kHz is kilohertz. Notice the capitalization. It's the same thing as kB versus kb.

Re:Only 90%?

[Anonymous Coward]

Incorrect. In any case, adding Curcurmin to the mix would solve that
problem -- http://www.tribuneindia.com/2001/20010221/cth3.htm [tribuneindia.com] .

http://www.thepowerhour.com/curcumin/Turmeric.pdf [thepowerhour.com] (warning pdf)

I love it.

Picky, picky.

[twitter]

There's not much to read besides abstracts and that's too bad. One of the abstracts said it well:

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.

Selective toxicity is what cancer treatment is all about, so while the sound man not "kill" cancer, it's a promising treatment.

It would be nice to see the actual studies. I'd like to see the statistics, and see if any other methods were tried and the researcher's reasoning. It may be that dysplastic cells are susceptible to sonic damage and this might work with other therapy methods, such as xray or heat. I'd also like to know how they treated prostate cancer, which is the number two cancer killer of men in the US.