Abstract
We have previously shown that carbon nanofibers (CNFs) and carbon nanotubes (CNTs) can sensitize prostate cancer (PCa) cells to platinum-based chemotherapeutics. In order to further verify this concept and to avoid a bias, the present study investigates the chemosensitizing potential of CNFs and CNTs to the conventional chemotherapeutics docetaxel (DTX) and mitomycin C (MMC), which have different molecular structures and mechanisms of action than platinum-based chemotherapeutics. DU-145 PCa cells were treated with DTX and MMC alone or in combination with the carbon nanomaterials. The impact of the monotreatments and the combinatory treatments on cellular function was then systematically analyzed by using different experimental approaches (viability, short-term and long-term proliferation, cell death rate). DTX and MMC alone reduced the viability of PCa cells to 94% and 68%, respectively, whereas a combined treatment with CNFs led to less than 30% remaining viable cells. Up to 17- and 7-fold higher DTX and MMC concentrations were needed in order to evoke a similar inhibition of viability as mediated by the combinatory treatments. In contrast, the dose of platinum-based chemotherapeutics could only be reduced by up to 3-fold by combination with carbon nanomaterials. Furthermore, combinatory treatments with CNFs led mostly to an additive inhibition of short- and long-term proliferation compared to the individual treatments. Also, higher cell death rates were observed in combinatory treatments than in monotreatments, e.g., a combination of MMC and CNFs more than doubled the cell death rate mediated by apoptosis. Combinations with CNTs showed a similar, but less pronounced impact on cellular functions. In summary, carbon nanomaterials in combination with DTX and MMC evoked additive to partly synergistic anti-tumor effects. CNFs and CNTs possess the ability to sensitize cancer cells to a wide range of structurally diverse chemotherapeutics and thus represent an interesting option for the development of multimodal cancer therapies. Co-administration of chemotherapeutics with carbon nanomaterials could result in a reduction of the chemotherapeutic dosage and thus limit systemic side effects.
Highlights
According to the global cancer statistics, prostate cancer (PCa) is the second most often diagnosed cancer in males worldwide and it ranks in fifth place among cancer-related deaths [1]
The present study investigated the influence of carbon nanofibers (CNFs) and carbon nanotubes (CNTs) co-exposed with DTX and mitomycin C (MMC) on cellular function of PCa cells in comparison to the individual effects
DTX and MMC concentrations of about 5 ng/mL and 0.75 μg/mL were needed (Supporting Information File 1, Figure S1a,b) to evoke comparable inhibition rates of 15% and 45% of 1.5 ng/mL DTX and 0.3 μg/mL MMC, respectively, in combination with 50 μg/mL CNTs (Table 1). This corresponded to a reduction down to approximately a third of the chemotherapeutic concentration when carbon nanomaterials were used in combination (Table 2)
Summary
According to the global cancer statistics, prostate cancer (PCa) is the second most often diagnosed cancer in males worldwide and it ranks in fifth place among cancer-related deaths [1]. Localized PCa is usually treated by surgical removal of the prostate (radical prostatectomy) or by radiation therapy Both treatment options are frequently associated with severe side effects such as incontinence and erectile dysfunction as well as gastrointestinal and genitourinary toxicity in case of radiation that result in a diminished quality of life [2]. Neoadjuvant chemotherapy is routinely used in the treatment of other solid tumors such as bladder, breast and colon cancer [3,4] To date it is not recommended for localized PCa by the current guidelines [2]. Several clinical trials have demonstrated the efficacy and safety of a neoadjuvant systemic chemotherapy with docetaxel (DTX) in combination with hormonal therapy prior to radical prostatectomy in patients with high-risk PCa [5,6,7]. In order to minimize systemic side effects, a local and precise application of chemotherapeutics to the PCa foci would be an alternative approach
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