Leaf extract of Osbeckia octandra induces apoptosis in oral squamous cell carcinoma cells

Jue Young Kim; Jin Kim; B M Ratnayake Bandara; Wanninayake M Tilakaratne; Dokyeong Kim

doi:10.1186/s12906-022-03505-4

Leaf extract of Osbeckia octandra induces apoptosis in oral squamous cell carcinoma cells

BMC Complement Med Ther. 2022 Jan 25;22(1):20. doi: 10.1186/s12906-022-03505-4.

Authors

Jue Young Kim^{1

2}, Jin Kim¹, B M Ratnayake Bandara³, Wanninayake M Tilakaratne^{4

5}, Dokyeong Kim^{6

7}

Affiliations

¹ Oral Cancer Research Institute, Department of Oral Pathology, Yonsei University College of Dentistry, Seoul, 03722, Republic of Korea.
² Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, 06230, Republic of Korea.
³ Department of Chemistry, Faculty of Science, University of Peradeniya, Peradeniya, 20400, Sri Lanka.
⁴ Department of Oral Pathology, Faculty of Dental Sciences, Center for Research in Oral Cancer, University of Peradeniya, Peradeniya, 20400, Sri Lanka.
⁵ Department of Oral Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, 50603, Malaysia.
⁶ Oral Cancer Research Institute, Department of Oral Pathology, Yonsei University College of Dentistry, Seoul, 03722, Republic of Korea. dkkim2908@gmail.com.
⁷ Precision Medicine Research Center, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. dkkim2908@gmail.com.

Abstract

Background: Osbeckia octandra is a plant endemic to Sri Lanka and is used in ethnomedicine for treating various diseases. However, the anti-cancer properties of O. octandra are yet to be fully investigated. In the present study, we evaluated the anti-cancer effects of O. octandra on oral cancer cells.

Methods: Human oral cancer cell lines (HSC2, YD10B, YD38, YD9, and YD32) were used in this study. BrdU incorporation, cell cycle and annexin-V/PI staining were all evaluated using flow cytometry to determine the extent to which O. octandra leaf extract inhibits cell proliferation and induces apoptosis. Cell viability and reactive oxygen species (ROS) were also measured in order to investigate the anti-cancer effects of O. octandra extracts. Western blotting was performed to detect cell cycle related protein such as cyclin d1 and cdk4, and to detect apoptosis-related proteins such as Bcl-2, Bcl-X_L, Bax, Caspase-9, Cleaved caspase-3, Fas, Caspase-8, and Bid.

Results: Leaf extract of O. octandra reduced oral squamous cell carcinoma (OSCC) cell viability in a dose-dependent manner. Leaf extract of O. octandra has non-toxic in normal keratinocytes. Also, O. octandra extract interrupted the DNA replication via G1 phase arrests, and this effect was independent of ROS generation. In the apoptosis-related experiments, the population of annexin V-positive cells increased upon treatment with O. octandra extract. Furthermore, the expression of anti-apoptotic protein (Bcl-2 and Bcl-xL) was decreased, whereas the expression of cleaved caspase-3 protein was increased in O. octandra-treated OSCC cells.

Conclusions: The results suggest that a leaf extract of O. octandra inhibited the proliferation of OSCC cells through G₁ phase arrest and interrupting DNA replication. The leaf extract of O. octandra could trigger the apoptotic response via caspase 3 activation in OSCC cells. These results suggest that O. octandra has the potential to be developed as an alternative medicine for treating OSCC.

Keywords: Apoptosis; Cell cycle arrest; Oral squamous cell carcinoma; Osbeckia octandra.

MeSH terms

Antineoplastic Agents, Phytogenic / pharmacology*
Antineoplastic Agents, Phytogenic / therapeutic use
Apoptosis / drug effects
Carcinoma, Squamous Cell / drug therapy*
Cell Line, Tumor / drug effects
Humans
Mouth Neoplasms / drug therapy*
Myrtales*
Phytotherapy
Plant Extracts / pharmacology*
Plant Extracts / therapeutic use
Sri Lanka

Substances

Antineoplastic Agents, Phytogenic
Plant Extracts