Anis Irmawati, Rasha Fatimah Abdullah, Athallah Reyhan Darmawan, Retno Indrawati Roestamadji, Ira Arundina, Noor Faizah Balqis, Fiki Muhammad Ridho, Noeroel Widajati, Raed Labib
Moderate-intensity exercise restored caspase-8 and caspase-9 expression suppressed by DMBA exposure, suggesting preservation of apoptotic signaling in DMBA-induced Wistar rats.
BACKGROUND: Oral squamous cell carcinoma (OSCC) accounts for approximately 90% of oral cancers, with tobacco exposure representing one of its major risk factors. The tobacco carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) induces oral epithelial dysplasia, a premalignant lesion. Caspase-8 and caspase-9 are initiator caspases that trigger apoptosis in dysplastic cells. Currently, disease management focuses on prevention. Moderate-intensity exercise has been reported to modulate apoptosis-related signaling and may contribute to cancer prevention.
OBJECTIVE: To evaluate the potency of moderate-intensity exercise on caspase-8 and -9 expression in a DMBA-induced oral dysplasia rat model.
METHODOLOGY: A total of 24 Wistar rats were randomly divided into four groups: K1 (no exercise, no DMBA), K2 (exercise, no DMBA), K3 (no exercise, DMBA), K4 (exercise, DMBA). Exercise consisted of moderate-intensity swimming at 70% MWC, performed 3x/week for 6 weeks. DMBA (0.02 mg/kg body weight) was injected into the buccal mucosa of the canine region twice weekly for 2 weeks. At the 7th week, the rats were anesthetized with ketamine (10 mg/kg body weight), euthanized by cervical dislocation, and buccal tissue specimens were collected. Immunohistochemical staining was performed to obtain caspase-8 and -9 expression. Data were analyzed in SPSS version 29.0.
RESULTS: All groups presented significant differences in caspase-8 (p = 0.004) and caspase-9 (p <0.001) expression. Caspase-8 and caspase-9 expression was significantly higher in K4 than in K3, with expression restored to levels comparable to the untreated control group (K1).
CONCLUSION: Moderate-intensity exercise restored caspase-8 and caspase-9 expression suppressed by DMBA exposure, suggesting preservation of apoptotic signaling in DMBA-induced Wistar rats.