Selective induction of apoptosis of human oral cancer cell lines by avocado extracts via a ROS-mediated mechanism
Haiming Ding1, Chunhua Han, Dongmei Guo
1Department of Radiology, College of Medicine, 460 W 12th Avenue BRT 714, The Ohio State University, Columbus, Ohio 43210, USA. ding.29@osu.edu
Abstract:
Avocados have a high content of phytochemicals with potential chemopreventive activity. Previously we reported that phytochemicals extracted from avocado meat into a chloroform partition (D003) selectively induced apoptosis in cancer but not normal, human oral epithelial cell lines. In the present study, we observed that treatment of human oral cancer cell lines containing high levels of reactive oxygen (ROS) with D003 increased ROS levels twofold to threefold and induced apoptosis. In contrast, ROS levels increased only 1.3-fold, and apoptosis was not induced in the normal cell lines containing much lower levels of basal ROS. When cellular ROS levels in the malignant cell lines were reduced by N-acetyl-l-cysteine (NAC), cells were resistant to D003 induced apoptosis. NAC also delayed the induction of apoptosis in dominant negative FADD-expressing malignant cell lines. D003 increased ROS levels via mitochondrial complex I in the electron transport chain to induce apoptosis. Normal human oral epithelial cell lines transformed with HPV16 E6 or E7 expressed higher basal levels of ROS and became sensitive to D003. These data suggest that perturbing the ROS levels in human oral cancer cell lines may be a key factor in selective apoptosis and molecular targeting for chemoprevention by phytochemicals.
Insights
Avocado phytochemicals selectively induce apoptosis in oral cancer cells by increasing reactive oxygen species (ROS). Reducing ROS levels protects cancer cells, suggesting ROS modulation as a chemoprevention strategy.
Area of Science:
- Phytochemistry
- Molecular Biology
- Cancer Research
Background:
- Avocado phytochemicals possess potential chemopreventive properties.
- Previous research indicated selective apoptosis induction in cancer cells by avocado extract (D003).
Purpose of the Study:
- To investigate the role of reactive oxygen species (ROS) in D003-induced apoptosis in oral cancer cells.
- To explore the potential of ROS modulation for chemoprevention strategies.
Main Methods:
- Treatment of oral cancer and normal oral epithelial cell lines with avocado extract (D003).
- Measurement of reactive oxygen species (ROS) levels.
- Assessment of apoptosis induction.
- Intervention with N-acetyl-l-cysteine (NAC) to reduce ROS levels.
- Analysis of D003 effects on HPV16 E6/E7 transformed cells.
Main Results:
- D003 significantly increased ROS levels and induced apoptosis in oral cancer cells, but not normal cells.
- Reducing ROS levels with NAC rendered cancer cells resistant to D003-induced apoptosis.
- D003-induced apoptosis was linked to increased ROS via mitochondrial complex I.
- Normal cells transformed with HPV16 E6/E7, exhibiting higher basal ROS, became sensitive to D003.
Conclusions:
- Perturbing ROS levels is a key mechanism for selective apoptosis induction by avocado phytochemicals in oral cancer.
- Targeting ROS levels presents a promising molecular strategy for chemoprevention of oral cancer.
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