Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases, and for the most cancer-related deaths. The survival pathway of Akt, its downstream effectors, the mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase (p70 S6K), and the Ras-extracellular signal-regulated kinase (Erk1/2) pathways are activated in cancer leading to cell survival and growth. Thus, approaches that inhibit these signaling molecules may prove useful in the fight against lung cancer. Exercise is associated with health benefits and a limited number of studies indicate that serum from physically active individuals inhibit mammary and prostate cancer cell growth. In this study, we examined the effects of post exercise serum on proliferation, survival, and signaling cascades of human NSCLC cells. Blood was collected from male subjects prior to, 5 min, 1 h, and 24 h after a single bout of high intensity interval exercise on a cycle ergometer. Exposure of NSCLC cells to post exercise serum resulted in the inhibition of cell proliferation and survival, as well as significant reduction of phosphorylated/activated Akt, mTOR, p70 S6K, and Erk1/2 levels compared to cells treated with serum taken pre-exercise. Our data suggest that post exercise serum has anti-cancer properties in lung cancer and deserves further systematic investigation in animal models.

This study examined potential exercise-induced changes in sclerostin and in bone turnover markers in young women following two modes of high intensity interval exercise that involve impact (running) or no-impact (cycling). Healthy, recreationally active, females (n=20; 22.5±2.7 years) performed two exercise trials in random order: high intensity interval running (HIIR) on a treadmill and high intensity interval cycling (HIIC) on a cycle ergometer. Trials consisted of eight 1 min running or cycling intervals at ≥90% of maximal heart rate, separated by 1 min passive recovery intervals. Blood samples were collected at rest (pre-exercise) and 5 min, 1h, 24h, and 48h following each exercise trial. Serum was analyzed for sclerostin, cross linked telopeptide of type I collagen (CTXI), and procollagen type I amino-terminal propeptide (PINP). A significant time effect was found for sclerostin, which increased from pre-exercise to 5 min after exercise in both trials (100.2 to 131.6 pg/ml in HIIR; 102.3 to 135.8 pg/ml in HIIC, p<0.001) and returned to baseline levels by 1h, with no difference between exercise modes and no exercise mode-by-time interaction. CTXI did not significantly change following either trial. PINP showed an overall time effect following HIIR, but none of the post hoc pairwise comparisons were statistically significant. In young women, a single bout of high intensity exercise induces an increase in serum sclerostin, irrespective of exercise mode (impact versus no-impact), but this response is not accompanied by a response in either bone formation or resorption markers.

This study examined resting levels of catabolic and anabolic osteokines related to Wnt signaling and their responses to a single bout of plyometric exercise in child and adolescent females. Fourteen premenarcheal girls [10.5 (1.8) y old] and 12 postmenarcheal adolescent girls [15.0 (1.0) y old] performed a plyometric exercise trial. One resting and 3 postexercise blood samples (5 min, 1 h, and 24 h postexercise) were analyzed for sclerostin, dickkopf-1 (DKK-1), osteoprotegerin (OPG), receptor activator of nuclear factor kappa-β ligand (RANKL), and transforming growth factors (TGF-β1, TGF-β2, and TGF-β3). Premenarcheal girls had significantly higher resting sclerostin, TGF-β1, TGF-β2, and TGF-β3 than the postmenarcheal girls, with no significant time effect or group-by-time interaction. DKK-1 was higher in premenarcheal compared with postmenarcheal girls. There was an overall significant DKK-1 decrease from baseline to 1 h postexercise, which remained lower than baseline 24 h postexercise in both groups. There was neither a significant group effect nor group-by-time interaction in OPG, RANKL, and their ratio. RANKL decreased 5 min postexercise compared with baseline and remained significantly lower from baseline 24 h following the exercise. No changes were observed in OPG. OPG/RANKL ratio was significantly elevated compared with resting values 1 h postexercise. In young females, high-impact exercise induces an overall osteogenic effect through a transitory suppression of catabolic osteokines up to 24 h following exercise.

Introduction/Purpose: To examine whether fluctuations in training load during an Olympic year lead to changes in bone mineral densities and factors that regulate bone (sclerostin, osteoprotegerin and receptor activator of nuclear factor kappa-B ligand), energy metabolism (insulin-like growth factor-1 and leptin), and inflammation (tumor necrosis factor-α and interleukin 6) in elite heavyweight female rowers. Methods: Blood samples were drawn from 15 female heavyweight rowers (27.0 ± 0.8 yr, 80.9 ± 1.3 kg, 179.4 ± 1.4 cm) at baseline (T1—45 wk before Olympic Games) and after 7, 9, 20, 25, and 42 wk (T1–6, respectively). Ongoing nutritional counseling was provided. Total weekly training load was recorded over the week before each time point. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry at T1 and T6. Results: Total BMD increased significantly before to after training (+0.02 g·cm⁻²), but was below the least significant change (±0.04 g·cm⁻²). Osteoprotegerin, insulin-like growth factor-1, and leptin remained stable across all time points. Fluctuations in training load (high vs low) were accompanied by parallel changes in tumor necrosis factor-α (2.1 ± 0.2 vs 1.5 ± 0.2 pg·mL⁻¹), interleukin 6 (1.2 ± 0.08 vs 0.8 ± 0.09 pg·mL⁻¹), and sclerostin (high: 993 ± 109 vs low: 741 ± 104 pg·mL⁻¹). Conclusions: In this population of young female athletes with suitable energy availability, sclerostin and inflammation markers responded to fluctuations in training load, whereas BMD and bone mineral content were stable during the season, suggesting that training load periodization is not harmful for the bone health in athletes.