Hyperthermia (HT) cancer treatments have been widely utilised, however, cancer cells develop thermotolerance following exposure to HT, and heat shock proteins (HSPs) are responsible for thermotolerance. A plant flavonoid, quercetin (QCT), has been reported to inhibit heat dependent expression of HSPs. In this study, therefore, the effects of prior exposure to QCT followed by HT on the cytotoxic and apoptotic activities were evaluated in FM3A, mouse breast cancer cells. Treatment of FM3A cells to 10 μM QCT and hyperthermia at 43°C for 1 h (HT) suppressed cell proliferation only in 34% and 55%, respectively and were relatively ineffective. Combination of the two treatments (QCT+HT) synergistically inhibited cell proliferation (90% inhibition). QCT+HT also suppressed clonogenicity (80%), compared to the results of QCT (56%) and HT (41%). Apoptotic cell death occurred after each treatment in a time-dependent manner. There was 4.9 ± 0.7%, 9.6 ± 1.5% and 18.1 ± 4.3% apoptosis after QCT+HT, and 3.2 ± 0.2%, 4.6 ± 0.5% and 8.6 ± 2.8% apoptosis after QCT, 3.4 ± 0.1%, 5.1 ± 0.3% and 10.1 ± 3.1% apoptosis after HT 1, 6 and 24 h post exposure compared to control of 2.0 ± 0.1%. HT or QCT proved ineffective in suppressing cell proliferation or inducing apoptosis. QCT+HT induced an accumulation of cells in G2/M and S phases and a reduction in G0/G1phase. The increased FM3A cell killing by HT after prior exposure to QCT is probably due to suppressed HSPs expression and diminished cellular thermotolerance. QCT may play a useful adjunct role in the hyperthermic treatment of resistant tumor.
The antineoplastic agent paclitaxel (PTX), a microtubule-stabilizing agent, is known to arrest cell cycle progression and induce apoptosis. Mild hyperthermia (HT) also disrupts the microtubule system and triggers apoptosis. We therefore investigated whether concurrent exposure of murine breast cancer cells to 10 µmol/l PTX and 43°C HT will promote improved anticancer effects. To do this, we exposed FM3A murine cancer cells to: (1) 10 µmol/l PTX for 1 h at 37°C followed by exposure at 43°C HT for 1 h; (2) 10 µmol/l PTX at 37°C for 2 h; (3) 37°C for 1 h followed by 43°C HT for 1 h, and (4) untreated cells at 37°C for 2 h which served as the control. Treatment No. 1 resulted in an enhanced cell cycle arrest, apoptosis and cytotoxicity. Exposure to 43°C HT alone or 10 µmol/l PTX alone induced lesser apoptosis and cytotoxicity than the two treatments concurrently applied. The apoptotic cell death occurred in a time-dependent manner as follows: (1) concurrently applied 43°C HT and 10 µmol/l PTX (5.6 ± 0.5, 16.5 ± 2 and 27.6 ± 1%); (2) 43°C HT alone (4.3 ± 1, 6.6 ± 0.3 and 12.7 ± 1%) and (3) 10 µmol/l PTX alone (4.4 ± 0.3, 8.6 ± 1 and 12.8 ± 1%) at 1, 6 and 24 h postexposure respectively compared to control of 2.0%. These data indicate that while both HT and PTX can individually induce apoptosis and antiproliferation in FM3A cancer cells, they may offer synergistic benefits when used concurrently.
Abstract Background For longitudinal melanonychia, clinical and dermoscopic criteria for differentiating malignant melanoma in situ from benign nevus/lentigo/functional melanonychia have not been fully established. Objective To propose a clinical classification of longitudinal melanonychia that is useful in judging the need for follow‐up. Methods A total of 137 patients with longitudinal melanonychia referred to our outpatient clinic in the most recent eight years were included. The mean and median lengths of follow‐up for patients were 5.0 and 5.5 years, respectively. We classified the 137 lesions into three types by clinical and dermoscopic features of the nail and periungual skin, including Hutchinson sign, variation of color, and borders in the pigmentation band. We observed type I and II lesions with dermoscopy every six months and three months, respectively. Results After follow‐up, all 72 lesions classified as type I were thought to be benign nevus/lentigo/functional melanonychia. Five of the 52 lesions classified as type II showed enlargement during follow‐up, and biopsy was performed. Of these five lesions, three were diagnosed as nevus/lentigo, and the other two were diagnosed as malignant melanoma in situ . All 13 lesions classified as type III were diagnosed as malignant melanoma in situ . Conclusion We can expect a type I lesion to be a benign nevus/lentigo/functional melanonychia and a type III lesion to be a malignant melanoma in situ ; however, type II lesions fall in a gray zone. We believe this classification is useful in deciding treatment and follow‐up.
