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Avicequinone B sensitizes anoikis in human lung cancer cells
Arisara Prateep1, Somruethai Sumkhemthong1, Wiranpat Karnsomwan2
1Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
Background:
During metastasis, cancer cells require anokis resistant mechanism to survive until reach the distant secondary tissues. As anoikis sensitization may benefit for cancer therapy, this study demonstrated the potential of avicequinone B, a natural furanonaphthoquinone found in mangrove tree (Avicenniaceae) to sensitize anoikis in human lung cancer cells.
Methods:
Anoikis inducing effect was investigated in human lung cancer H460, H292 and H23 cells that were cultured in ultra-low attachment plate with non-cytotoxic concentrations of avicequinone B. Viability of detached cells was evaluated by XTT assay at 0-24 h of incubation time. Soft agar assay was performed to investigate the inhibitory effect of avicequinone B on anchorage-independent growth. The alteration of anoikis regulating molecules including survival and apoptosis proteins were elucidated by western blot analysis.
Results:
Avicequinone B at 4 μM significantly induced anoikis and inhibited proliferation under detachment condition in various human lung cancer cells. The reduction of anti-apoptotic proteins including anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia 1 (Mcl-1) associating with the diminution of integrin/focal adhesion kinase (FAK)/Proto-oncogene tyrosine-protein kinase (Src) signals were detected in avicequinone B-treated cells.
Conclusions:
Avicequinone B sensitized anoikis in human lung cancer cells through down-regulation of anti-apoptosis proteins and integrin-mediated survival signaling.
Insights
Avicequinone B, a natural compound, sensitizes human lung cancer cells to anoikis, a key process in metastasis. This compound reduces survival signals, offering potential for new cancer therapies.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Cancer cells develop anoikis resistance to survive during metastasis.
- Sensitizing cancer cells to anoikis is a potential therapeutic strategy.
- Avicequinone B, a natural furanonaphthoquinone from mangroves, was investigated for its anoikis-sensitizing potential.
Purpose of the Study:
- To investigate the potential of avicequinone B to sensitize human lung cancer cells to anoikis.
- To evaluate the effect of avicequinone B on cancer cell viability and anchorage-independent growth.
- To elucidate the molecular mechanisms underlying avicequinone B-induced anoikis.
Main Methods:
- Human lung cancer cell lines (H460, H292, H23) were cultured in ultra-low attachment plates with avicequinone B.
- Cell viability was assessed using XTT assay.
- Anchorage-independent growth was evaluated by soft agar assay.
- Western blot analysis was used to examine anoikis-regulating proteins.
Main Results:
- Avicequinone B (4 μM) significantly induced anoikis and inhibited proliferation in detached lung cancer cells.
- Treatment with avicequinone B led to reduced levels of anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia 1 (Mcl-1).
- Avicequinone B diminished integrin/focal adhesion kinase (FAK)/Proto-oncogene tyrosine-protein kinase (Src) signaling pathways.
Conclusions:
- Avicequinone B effectively sensitizes human lung cancer cells to anoikis.
- The mechanism involves down-regulation of anti-apoptotic proteins.
- Avicequinone B also inhibits integrin-mediated survival signaling, contributing to anoikis sensitization.
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