Synergistic inhibitory effects of capsaicin combined with cisplatin on human osteosarcoma in culture and in xenografts

Abstract

BackgroundThe combination of phytochemicals with chemotherapy drugs is an emerging new strategy for cancer therapy to increase antitumor responses.MethodsThe present study investigates the effect of the combination of capsaicin (CAP) with cisplatin (DDP) and the potential underlying anticancer mechanisms in osteosarcoma (OS) cells in vitro and in vivo.ResultsCell viability assays and isobolographic analyses demonstrated that the combination of CAP and DDP showed synergistic cytotoxic effects on OS cells. We chose relatively low concentrations of CAP (100 μM) and DDP (16.7 μM) for subsequent experiments. Generally, the combination of CAP and DDP had significant effects on apoptosis induction, cell cycle arrest and cell invasion inhibition in OS cells compared with the individual-treatment groups and the control group. Moreover, cotreatment with CAP and DDP triggered prosurvival autophagy through reactive oxygen species (ROS)/JNK and p-AKT/mTOR signaling in OS cells. The combination regimen of CAP and DDP also inhibited tumor growth in an OS xenograft model.ConclusionThese results suggest that the combination of CAP and DDP has strong inhibitory effects on OS cells and identify CAP as a promising agent for supplementing standard chemotherapy and possible future targeted therapy in OS.

Bruceine D inhibits tumor growth and stem cell‐like traits of osteosarcoma through inhibition of STAT3 signaling pathway

“…[37][38][39] Induction of cell cycle arrest is an important mechanism through which chemo-drugs exert their anti-cancer activities. 40 Our results indicate that treatment of BD could induce cell cycle arrest and suppress proliferation of osteosarcoma cells. Cell cycle progression is controlled by a number of cyclin-dependent kinases (CDK) and their regulatory partners, the cyclins.…”

“…Anomaly in cell cycle progression underlies the unscheduled cell proliferation that characterizes cancer . Induction of cell cycle arrest is an important mechanism through which chemo‐drugs exert their anti‐cancer activities . Our results indicate that treatment of BD could induce cell cycle arrest and suppress proliferation of osteosarcoma cells.…”

Norcantharidin inhibits proliferation and promotes apoptosis via c‐Met/Akt/mTOR pathway in human osteosarcoma cells

“…After the mice were acclimated for 1 week prior to study initiation, 100 μL of HOS cells at a density of 2 × 10 6 cells/mL were injected into the right flank. Tumor volume (TV) was measured daily and calculated according to the following formula: TV (mm 3 ) = 0.5 × ab 2 (where a is the longest diameter and b is the shortest diameter of the tumor) . When the average TV in all animals reached approximately 100 mm 3 , the nude mice were randomly assigned to 2 groups (with 6 nude mice/group).…”

“…NCTD, norcantharidin; OS, osteosarcoma measured daily and calculated according to the following formula: TV (mm 3 ) = 0.5 × ab 2 (where a is the longest diameter and b is the shortest diameter of the tumor). 10 When the average TV in all animals reached approximately 100 mm 3 , the nude mice were randomly assigned to 2 groups (with 6 nude mice/group). The NCTD groups received an intraperitoneal injection of 25 mg/kg NCTD every 2 days, while the control group was administered saline.…”

Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma

“…Phytochemicals are naturally occurring plant-derived compounds that have been widely used to treat a variety of malignant tumors due to their availability, biological activity, and nontoxic effects [4]. Emerging evidence suggests that numerous phytochemicals can reverse the resistance of various malignancies to cisplatin while counteracting organ toxicity caused by cisplatin [5][6][7]. Thus, in many types of malignancies, phytochemicals are candidates for overcoming cisplatin resistance.…”