Background
Oral cancer is the sixth most common cancer in the world [
1,
2]. Oral cancer is easy to detect clinically but is frequently ignored by patients resulting in high mortality rates [
3]. Although several oral tumor markers have been reported [
4,
5], these efforts focused on detection rather than therapy and effective anti-oral cancer therapies are still needed.
Cryptocarya (family Lauraceae) is widely found in the tropics and subtropics [
6]. Its crude extracts have been demonstrated to have an antiproliferative ability against cancer. For example, methanolic extracts of the leaves of
C. griffithiana and the roots of
C. concinna can inhibit cell proliferation of human HL60 promyelocytic leukemia cells [
7] and oral cancer cells [
8], respectively. The ethanolic extracts of the fruit and trunk bark of
C. obovata have been reported to have an antiproliferative effect against human KB cells [
9].
Several
Cryptocarya-derived compounds have been found to have diverse biological functions, i.e., anti-dengue virus by alkylated flavanones [
10], anti-HIV by phenanthroindolizidine alkaloids [
11], anti-tuberculosis by pinocembrin [
12], anti-plasmodial by (+)-N-methylisococlaurine, atherosperminine, and 2-hydroxy-atherosperminine [
13], anti-trypanosomal by 7′,8′-dihydroobolactone [
14], and anti-inflammatory by (2S)-5,7-dihydroxyflavanone and cryptocaryanone B [
15].
Recently,
Cryptocarya-derived compounds have been reported to have an antiproliferation effect on cancer. For example, the proliferation of leukemia cells was inhbitied by
C. costata-derived 2′,4′-dihydroxy-5′,6′-dimethoxychalcone and isodidymocarpin [
16] and
C. konishii-derived by desmethylinfectocaryone, infectocaryone, and cryptocaryone (CPC) [
17]. Among these
Cryptocarya-derived compounds, we are interested in the anticancer effect of CPC, which is one of the major constituents in the commonly distributed evergreen plant
C. concinna in Taiwan [
18].
Although the anticancer effect of CPC, a kind of dihydrochalcone, had been reported in some cancer types such as murine leukemia [
17] and prostate cancer [
19], few studies have addressed its antiproliferative effect on oral cancer. Moreover, the cell killing mechanism of cryptocaryone in cancer remains unclear. Recently, reactive oxygen species (ROS) generation was reported to be involved in
Corema album-derived dihydrochalcone induced cytotoxicity for colon cancer cells [
20]. Accordingly, the relationship between ROS generation and CPC effect for oral cancer cells is worth examining.
This study evaluates possible anticancer functions of CPC and explores its drug mechanisms in terms of cell viability, cell cycle analysis, apoptosis, ROS generation, mitochondrial depolarization, and DNA damage detection. The role of oxidative stress in CPC’s effect on oral cancer cells is also addressed.
Acknowledgements
This work was supported by funds of the Ministry of Science and Technology (MOST 104-2320-B-037-013-MY3, MOST 103-2314-B-037-010-MY3, MOST 103-2320-B-037-008, and NSC 101-2320-B-037-049), the Kaohsiung Medical University “Aim for the Top Universities Grant, grant No. KMU-TP103A33, KMU-TP103H01, KMU-TP103H05, and KMU-TP104PR02”, the National Sun Yat-sen University-KMU Joint Research Project (#NSYSU-KMU 105-P002), the Kaohsiung Municipal Ta-Tung Hospital (kmtth-104-003), the Kaohsiung Medical University Hospital (KMUH103-3M39), the Health and welfare surcharge of tobacco products, the Ministry of Health and Welfare, Taiwan, Republic of China (MOHW104-TDU-B-212-124-003 and MOHW105-TDU-B-212-134005), and ChiMei-KMU Joint Project (104CM-KMU-02). We thank the Center for Research Resources and Development of Kaohsiung Medical University for providing the service of Nuclear Magnetic Resonance. We also thank for the help in English editing by Dr. Hans-Uwe Dahms.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
H-SC, J-YT, and H-WC participated in the manuscript writing. M-YH and H-WC participated in the study design. I-SC identified and collected the materials C. concinna. H-SC prepared the CPC from C. concinna. H-WH instructed Y-AC to perform the flow cytometer and analyzed data. C-YW instructed Y-AC to perform the survival assay and analyzed data. J-YT, C-YY, and H-RW performed statistical analysis. M-YH and H-WC coordinated and oversaw the study. All authors read and approved the final manuscript.