Pseudolaric Acid B Induces Growth Inhibition and Caspase-Dependent Apoptosis on Head and Neck Cancer Cell lines through Death Receptor 5.

Abstract

Pseudolaric Acid B (PAB), diterpenoid isolated from the root bark of Pseudolarix kaempferi Gordon tree (Pinaceae), exhibits an anti-proliferative and apoptotic activity in various cancer cell lines but to date, the effects of PAB on head and neck cancer (HNC) cell lines remain to be elucidated. In this study, we showed that PAB significantly inhibited the viability and caspase-dependent apoptosis in HN22 cell line. PAB-induced apoptosis is through inducing death receptor 5 (DR5) together with the increase in the expression of cleaved caspase-8. It also inhibited the proliferations and induced apoptosis through DR5 in other three HNC cell lines (HSC3, Ca9.22, and HSC4). Extending our in vitro findings, we found that ethanol extract of Pseudolarix kaempferi (2.5 mg/kg/day) reduced tumor growth in a xenograft model bearing HN22 cell line without any change in body weight. DR5 were also found to be increased in tumors tissue of PAB-treated mice without any apparent histopathological changes in liver or kidney tissues. Taken together, PAB may be a potential lead compound for chemotherapeutic agents against head and neck cancer.

• Authors: Su-Jung Choi, Chi-Hyun Ahn, In-Hyoung Yang, Bohwan Jin, Won Woo Lee, Ji-Hoon Kim, Min-Hye Ahn, Neeti Swarup, Kyoung-Ok Hong, Ji-Ae Shin, Nam-Tae Woo, Seong Doo Hong, Jae-Il Lee, Sung-Dae Cho
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 24 Issue 20 (Oct 16 2019) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 31623058 (Publication Type: Journal Article)

Chemical References

• Diterpenes
• Drugs, Chinese Herbal
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• TNFRSF10B protein, human
• pseudolaric acid B

Topics

• Animals
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Disease Models, Animal
• Diterpenes (chemistry, pharmacology)
• Drugs, Chinese Herbal (chemistry, pharmacology)
• Head and Neck Neoplasms (metabolism)
• Humans
• Mice
• Molecular Structure
• Receptors, TNF-Related Apoptosis-Inducing Ligand (genetics, metabolism)
• Xenograft Model Antitumor Assays