Cosmos caudatus Leaf Extract Triggers Apoptosis of HSC-3 Cancer Cells by Decreasing Bcl-2 and Increasing Bax

Ferry Sandra, Muhammad Ihsan Rizal, Afifah Yumna Dhaniar, Alifah Evi Scania, Kyung Hoon Lee


BACKGROUND: Previous studies have demonstrated that Cosmos caudatus leaf extract (CCLE) exhibits cytotoxic effects against various types of human cancer. However, the CCLE cytotoxic effect towards oral squamous cell carcinoma (OSCC) cells has not been investigated. Therefore, this study was conducted to evaluate the effect of CCLE towards the viability and apoptosis in human oral squamous carcinoma (HSC)-3 cells.

METHODS: HSC-3 cells were treated with various concentrations of CCLE for 24 h. The number of viable HSC-3 cells were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), meanwhile the apoptotic HSC-3 cells were measured using sub-G1 assay. Mitochondrial membrane potential was measured using flow cytometry. Bcl-2 and Bax protein content of HSC-3 cells were measured using enzyme-linked immunosorbent assay (ELISA).

RESULTS: CCLE treatment could decrease the number of HSC-3 viable cells and increase the percentage of HSC-3 apoptotic cells in concentration-dependent manner. In mitochondrial membrane potential assay, CCLE-treated group displayed a peak shifment from 104 to 103. Bcl-2 protein contents of CCLE-treated group were decrease in concentration-dependent manner, meanwhile Bax protein contents of CCLE-treated group were increase in concentration-dependent manner.

CONCLUSION: CCLE could trigger apoptosis in HSC-3 cells by decreasing Bcl-2 protein content and increasing Bax protein content in concentration-dependent manner, leading to intrinsic apoptotic pathway.

KEYWORDS: Cosmos caudatus, HSC-3, apoptosis, mitochondrial membrane potential, Bcl-2, Bax

Full Text:



Efferth T. Editorial: Chemoprevention of cancer by natural products. Cancer Lett. 2019; 459: 13-14, CrossRef.

Rahman MN, Wijaya CR, Novalentina M. Survivin clinical features in cervical cancer. Mol Cell Biomed Sci. 2017; 1(1): 6-16, CrossRef.

Abotaleb M, Samuel SM, Varghese E, Varghese S, Kubatka P, Liskova A, et al. Flavonoids in cancer and apoptosis. Cancers. 2018; 11(1): 28, CrossRef.

Sulaiman CT, Balachandran I. Total phenolics and total flavonoids in selected indian medicinal plants. Indian J Pharm Sci. 2012; 74(3): 258-60, CrossRef.

Moshawih S, Cheeme MS, Ahmad Z, Zakaria ZA, Hakim MN. A comprehensive review on Cosmos caudatus (Ulam raja): Pharmacology, ethnopharmacology, and phytochemistry. Int Res J Educ Sci. 2017; 1(1): 14-31, article.

Cheng SH, Barakatun-Nisak MY, Anthony J, Ismail A. Potential medicinal benefits of Cosmos caudatus (Ulam raja): A scoping review. J Res Med Sci. 2015; 20(10): 1000-6, CrossRef.

Hermawati E, Handini M, In'am Ilmiawan M, Mahyarudin M. Chlorogenic acid protects cell death in the cerebellum through anti-apoptotic protein Bcl2 in transient global ischemia cases. Mol Cell Biomed Sci. 2024; 8(1): 44-50, CrossRef.

Ahda M, Jaswir I, Khatib A, Ahmed QU, Syed-Mohamad SNA. A review on Cosmos caudatus as A potential medicinal plant based on pharmacognosy, phytochemistry, and pharmacological activities. Int J Food Prop. 2023: 26(1): 344-58, CrossRef.

Chan EWC, Wong SK, Chan HT. Ulam herbs of Oenanthe javanica and Cosmos caudatus: An overview on their medicinal properties. J Nat Remedies. 2016; 16(4): 137-47, CrossRef.

Limanto A, Simamora A, Santoso AW, Timotius KH. Antioxidant, α-glucosidase inhibitory activity and molecular docking study of gallic acid, quercetin and rutin: A comparative study. Mol Cell Biomed Sci. 2019; 3(2), 67-74, CrossRef.

Deepika, Maurya PK. Health benefits of quercetin in age-related diseases. Mol. 2022; 27(8): 2498, CrossRef.

Fitriasih F, Komariyah SM, Sandra F, Pratiwi N, Hidayati DN. Mangifera indica L. Leaves extract induced intrinsic apoptotic pathway in MCF-7 cells by decreasing bcl-2 expression and inducing bax expression. Indones J Cancer Chemoprevent. 2019; 10(1): 1-6, CrossRef.

Sandra F, Nakamura N, Mitsuyasu T, Shiratsuchi Y, Ohishi M. Two relatively distinct patterns of ameloblastoma: an anti-apoptotic proliferating site in the outer layer (periphery) and a pro-apoptotic differentiating site in the inner layer (centre). Histopathology. 2001; 39(1): 93-8, CrossRef.

Adawiyah R, Setiawan A, Nita S. Pengaruh fraksi aktif dari ekstrak daun kenikir (Cosmos caudatus kunth) terhadap uji sitotoksik. Biomed J Indones. 2017; 3(3): 138-44, CrossRef.

Nurhayati B, Rahayu IG, Rinaldi SF, Zaini WS, Afifah E, Arumwardana S, et al. The antioxidant and cytotoxic effects of Cosmos caudatus ethanolic extract on cervical cancer. Indones Biomed J. 2018; 10(3): 243-49, CrossRef.

Wicaksono BD, Tangkearung E & Sandra F, Brucea javanica leaf extract induced apoptosis in human oral squamous cell carcinoma (HSC-2) cells by attenuation of mitochondrial membrane permeability. Indones Biomed J. 2015; 7(2): 107-10, CrossRef.

Sandra F, Sudiono J, Trisfilha P, Pratiwi D. Cytotoxicity of Alpinia galanga rhizome crude extract on NIH-3T3 cells. Indones Biomed J. 2017; 9(1): 23-8, CrossRef.

Sandra F, Rizal MI, Wahid AHA, Andajana M, Celinna M. Caffeic acid induces intrinsic apoptotic pathway in mg-63 osteosarcoma cells through bid truncation and cytochrome c release. Indones Biomed J. 2022; 14(3): 323-8, CrossRef.

Sandra F, Hendarmin L, Nakao Y, Nakamura N, Nakamura S. TRAIL cleaves caspase-8, -9 and -3 of AM-1 cells: A possible pathway for TRAIL to induce apoptosis in ameloblastoma. Tumour Biol. 2005; 26(5): 258-64, CrossRef.

Arung ET, Wicaksono BD, Handoko YA, Kusuma IW, Shimizu K, Yulia D, et al. Cytotoxic effect of artocarpin on T47D cells. J Nat Med. 2010; 64(4): 423-9, CrossRef.

Sajjadi SE, Ghanadian M, Haghighi M, Mouhebat L. Cytotoxic effect of Cousinia verbascifolia Bunge against OVCAR-3 and HT-29 cancer cells . J Herbmed Pharmacol 2015; 4(1): 15-19, article.

Tait SW, Parsons MJ, Llambi F, Bouchier-Hayes L, Connell S, Muñoz-Pinedo C, et al. Resistance to caspase-independent cell death requires persistence of intact mitochondria. Dev Cell. 2010; 18(5): 802-13, CrossRef.

Pires AS, Marques CR, Encarnação JC, Abrantes AM, Marques IA, Laranjo M, et al. Ascorbic acid chemosensitizes colorectal cancer cells and synergistically inhibits tumor growth. Front Physiol. 2018; 9: 911, CrossRef.

Nemec KN, Khaled AR. Therapeutic modulation of apoptosis: Targeting the BCL-2 family at the interface of the mitochondrial membrane. Yonsei Med J. 2008; 49(5): 689-97, CrossRef.

Massardi A, Bahry SS, Rahmawati NA, Shabirah CA, Pangastuti A. Bioactive compounds from Penicillium sp. inhibit antiapoptotic Bcl-2, Bcl-XL and Mcl-1: An in silico study. Mol Cell Biomed Sci. 2023; 7(2): 81-9, CrossRef.

Dini T, Nugraha Y, Revina R, Karina K. Safety and efficacy of mesenchymal stem cells in burn therapy: Systematic review. Mol Cell Biomed Sci. 2022; 6(3): 104-6, CrossRef.

Chien SY, Wu YC, Chung JG, Yang JS, Lu HF, Tsou MF, et al. Quercetin-induced apoptosis acts through mitochondrial- and caspase-3-dependent pathways in human breast cancer MDA-MB-231 cells. Hum Exp Toxicol. 2009; 28: 493-503, CrossRef.


Copyright (c) 2024 The Prodia Education and Research Institute

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.


Indexed by:






The Prodia Education and Research Institute