Biology, Medicine, & Natural Product Chemistry  ISSN 2089-6514 (paper) 
Volume 10, Number 2, October 2021 | Pages: 87-91 | DOI: 10.14421/biomedich.2021.102.87-91 ISSN 2540-9328 (online) 
 

 

 

 

Potential of Tithonia diversifolia Hemsley A. Gray (Kembang Bulan) 

Leaf Extract as Anti-Cancer Agents 

 
Muflihah Rizkawati 

Department of Pharmacology, Faculty of Medicine, Universitas Islam Indonesia, Indonesia. 

 

Corresponding author 
dr.rizkawati@uii.ac.id 

 

 
Manuscript received: 22 September 2021. Revision accepted: 04 October, 2021. Published: 07 October, 2021. 

 

 

Abstract 

 

The main objective of this review is to explain the great potential of herbal plants as anticancer agents. Cancer is a disease caused by 

abnormal cell growth in the body. The high number of cancer incidents still become a global concern because of the high mortality rate. 

The treatments of cancer such as chemotherapy can cause serious side effects by killing the normal cells. This is the reason why it is 

necessary to develop an alternative treatment of cancer. I discussed a plant that is believed to has health benefit. Many studies have 

showed the positive effect of Tithonia diversifolia plant for health. After 2000, the researchers discovered a new potential through its 

cytotoxicity to neoplastic cells. This plant needs to be developed sustainably. However, in the future this plant might become an effective 

alternative to treat cancer with lower side effects. 

 

Keywords: Tithonia diversifolia (Hemsley) A. Gray; Kembang bulan; Anticancer. 

 

 

INTRODUCTION 
 

Cancer is a disease with a multifactorial etiology which 

is initiated by an abnormal and uncontrolled expression 

of transcription factors. This can be affected by a gene 

mutation (Babazadeh et al., 2018). Cancer is one of the 

main causes of death in the world and still become a 

global concern. Cancer has the second highest risk of 

death with a mortality ratio of 1:6 or around 9.6 million 

deaths in 2018. The most common types of cancer in 

men are lung, prostate, colorectal, stomach, and liver 

and the most common types of cancer in women are 

breast, colorectal, lung, cervical and thyroid cancers 

(WHO, 2021). Cancer can develop in any part of the 

body and can spread (metastasize) to other parts of the 

body. Although some types of cancer can be similar in 

some ways, how they develop, grow, spread, and 

respond to drugs can be very different (American 

Cancer Society, 2021). 

The research and development data in 2019 showed 

the incidence of cancer in Indonesia reached 

136.2/100,000 population and reach 8th place in 

Southeast Asia. The highest incidence rate of cancer for 

men is lung cancer, which is 19.4 per 100,000 

population with an average death rate of 10.9 per 

100,000 population, while the highest incidence rate of 

cancer for women is breast cancer, which is 42.1 per 
100,000 population with an average 17 deaths per 

100,000 population (Kemenkes RI, 2019). 

Cancer treatment methods are still being developed. 

There are several types of local treatment such as 

surgery and radiation therapy, and systemic treatment 

such as chemotherapy, immunotherapy, or targeted 

therapy that can affect not only cancer cells but also the 

entire body (American Cancer Society, 2021). 

Understanding the causes, how they are formed, and 

especially the factors that promote or inhibit their 

growth required to solve the complex biological and 

medical problems. Currently, there are many successful 

results from cancer treatment. For example, over the 

past half century, the survival rate for childhood 

leukemia has increased from 10% to more than 80%. 

But the healing method (or extended remission) is 

difficult, and is only available to those who living in 

affluent countries. There is nothing like "medicine" for 

cancer, and much remains for medical researchers to do 

(Haussman, 2019). 

The cancer treatment ideally can stop the growth of 

cancer cells with a selective toxic effect on the targeted 

cancer cells without damaging other normal tissues. 

However, most of today's anticancer drugs are still 

potentially toxic to normal tissues. The condition can 

cause harmful side effects to the body. Therefore, the 

discovery of anti-cancer drugs that have more positive 

effects with low toxicity is being developed. Many 

potential phytopharmaceuticals have been investigated 

to find chemical elements in plants that are beneficial for 

treatment (Wahyuningsih et al., 2013). The development 

of herbal studies using in vitro and in vivo methods has 

https://doi.org/10.14421/biomedich.2021.102.87-91


 

 

 

88 Biology, Medicine, & Natural Product Chemistry 10 (2), 2021: 87-91 
 

 

shown the beneficial effects of medicinal plants and 

their bioactive compounds. The most common anti-

cancer mechanism is by inducing apoptosis in neoplastic 

cells. Currently, more than 25% of drugs used over the 

last 20 years are derived directly from plants. According 

to WHO, 80 percent of the world's population has 

benefited from traditional medicine (Aryan, 2018). 

Nowadays, the efforts to develop new anti-cancer 

medicines and particularly novel drug delivery systems 

should be done. It is important to improve the 

pharmacodynamics and bioavailability of drugs and to 

deliver specific drug concentration to cancer cells so it 

can produce minimum cytotoxic effects on normal cells 

(Babazadeh et al., 2018). 

 

 

Tithonia diversifolia CHARACTERIZATION 
 

The Asteraceae family is known for its therapeutic effect 

such as antihelmintic, anti-inflammatory, astringent, 

antispasmodics, cholesteric, antioxidant, anti-

hemorrhagic, antimicrobial, diuretics, and analgesics. 

One type of the species from this family is Tithonia 

diversifolia (Farias et al., 2019). T. diversifolia can be 
described as a flowering shrub-like species, growing up 

to over 2–3 m high. The flowers are 5–15 cm wide and 

shaped like a daisy. The leaves (15–30 cm long) can be 

described as sub-ovale, petiolate, 3- to 7-lobed delicately 

hairy, and alternately to oppositely arranged (Tagne at 

al., 2018). T. diversifolia (Hemsl.) A. Gray (Mexican 
sunflower) originally from Mexico and Central America, 

but is now widely known in various parts of the world as 

an ornamental plant and a plant used for medicine. 

There are more than 150 types of secondary metabolites 

isolated from T. diversifolia, including the sesquiterpene 
lactones thyrotundin, tagitinin A, and tagitinin C 

(Miranda et al., 2015). T. diversifolia can be found in 

tropical and subtropical climes. Traditionally, all parts of 

the plant especially the leaves, are used by people to 

treat wounds, musculoskeletal disorders, abscesses, 

dermatological conditions, stomach pains, oral treatment 

for diabetes, malaria, fever, hepatitis and infectious 

diseases. Some studies showed the heterogenous 

evidence from in vitro and in vivo research that 

supporting most of the traditional therapeutic claims. T. 
diversifolia can grow up for all year-round and used 

fresh or dry as traditional remedies in several cultures. 

All parts of the plant are useful include the leaves, 

flowers, stems and roots are mentioned in some 

ethnobotanical reports (Tagne et al., 2018). 

The studies on phytochemical screening not only 

showed the presence of metabolites phenolics, 

flavonoids and tannins but also absence of alkaloids and 

saponins in T. diversifolia ethanolic flower extract. 

Phenolics are well known for their antioxidants and 

antimicrobial properties. This plays a role in prevention 

activities of phenolic against infection and degenerative 

disease, inflammation and allergies through 

antioxidants, antimicrobial and protein or enzyme 

neutralization or modulation mechanism. The examples 

of phenolic compounds are flavonoids and tannins. 

Flavonoids have many beneficial health effect and 

physiological properties. Flavonoids have antioxidant 

effects, anti-inflammatory, anti-mutagenic, anti-

carcinogenic property and as a modulator to the function 

of cellular enzymes. It is also have a great potensial 

inhibitors of xanthine oxidase, cyclooxygenase, 

lipoxygenase and phosphoinositide 3-kinase. Tannins 

has antioxidant, anticarcinogenic and antimutagenic 

potential. Tannins are also known to accelerate blood 

clotting, lower blood pressure, lower serum lipid levels 

and modulation of immunoresponse. Terpenoids has an 

antibiotic, chemopreventive and therapeutic effects on 

cancer. Terpenoids have been developed in the 

prevention, inhibition and therapy of several diseases 

including cancer, antivirals, antimicrobial, anti-allergic, 

antispasmodic, antidiabetic, anti-inflammatory, 

anticancer and immuno-modulatory properties (Gaule 

Ang et al., 2019).  

Farias et al, in 2019 also evaluate the composition, 

antioxidant, cytotoxic and microbiological activity of the 

essential oil of the leaves of the species T. diversifolia. 
The main constituent they was found are α-pinene 

(9.9%), Limonene (5.40%), (Z)-β-ocimene (4.02%), p-

cymen-8-ol (3.0%), Piperitone (11.72%), (E)-nerolidol 

(3.78%) and Spathulenol (10.8%). The activity of 

antioxidant from thee essential oil extracted from the 

leaves of T. diversifolia can be observed from the 
significant result with p < 0.0001 at the concentration of 

5 mgmL-1 with %AA 54.6 ± 0.06. The minimum 

inhibitory concentration (IC50) was 4.30 mgmL-1 , with 

a strong correlation coeffificient (R2) of 0.9965. 

Although T. diversifolia has good antioxidant activity, 
its IC value still lower than ascorbic acid (Farias et al., 

2019).  

 

 

ANTI-CANCER POTENTIAL  
 

Activity-guided fractionation technique of an ethyl 

acetate extract from T. diversifolia, using an 
antiproliferative bioassay against human colon cancer 

cells (Col2), resulted in the isolation of three new 

sesquiterpenoids, 2R-hydroxytirotundin (1), 

tithofolinolide (2), and 3R-acetoxydiversifolol. (3), 

together with eight known sesquiterpene lactones, 3'-

acetoxy-8'-isobutyryloxyreynosine (4), tagitinin C (5), 

1',2Repoxytagitinin C (6), 4R,10R-dihydroxy-3-oxo-8'-

isobutyryloxyguaia -11(13)-en-12,6R-olide (7), 3R-

acetoxy4R-hydroxy-11(13)-eudesmen-12-oic acid 

methyl ester, 17,20-dihydroxygeranylnerol, tagitinin A, 

and thyrotundine. Measurement of antiproliferative 

activity in Col2 cells and induction of cellular 

differentiation in human promyelocytic leukemia (HL-

60) cells were carried out to determine the potential of 

these isolates as cancer chemopreventive agents. In this 



 

 

 

 Rizkawati – Potential of Tithonia diversifolia as Anti-Cancer Agents 89 
 

 

study, a culture test was used on rat breast organs that 

had been induced by 7,12-dimethylbenz[a]anthracene 

and the selected compound was tested for its ability to 

inhibit preneoplastic lesions. Isolates tagitinin C and 1',2 

Repoxytagitinin C showed significant antiproliferative 

activity. Isolat tithofolinolide, 3'-acetoxy-8'-

isobutyryloxyreynosine, and 4R,10R-dihydroxy-3-oxo-

8'-isobutyryloxyguaia -11(13)-en-12,6R-olide induced 

cellular differentiation of HL-60. The isolate 3'-acetoxy-

8'-isobutyryloxyreynosine significantly inhibited (63.0% 

at 10 μgmL-1) lesion formation in rat breast organ 

culture assays. Among these isolates there were several 

sesquiterpenoids and flavonoids that showed anti-human 

pro myelocytic leukemia (HL-60) activity and Tagitinin 

C was the main sesquiterpenoid that had been identified 

(Gu et al., 2002).  

The methanol extract of Tithonia diversifolia showed 
antiproliferative activity against glioblastoma cells 

U373, with an IC50 value of 59.2 ±3.7 μgmL
-1, while 

tagitinin C showed an IC50 value of 6.1 ±0.1 μgmL
-1. 

Based on flow cytometric analysis and pan-caspase 

inhibitory activity, the anti-glioblastoma effect was 

independent of apoptosis and it was concluded that 

tagitinin C induces U373 cell death through autophagy 

under certain conditions. Autophagy is a transport 

pathway to all eukaryotic cells. Cells degrade part of 

their own intracellular constituents, including cytoplasm 

and organelles. The first process for autophagi 

mechanism is the formation of a double membrane 

bound vacuole from endoplasmic reticulum. The 

autophagosomes receive hydrolases to form an 

autolysosome. This study also found that human 

glioblatoma U373 cell death induced by tagitinin C was 

apoptosis-independent and induced autophagosome (Lee 

at al., 2011). 

Another study showed the activity of the extract T. 

diversifolia in inhibiting the viability of keloid 

fibroblasts. Antifibrotic activity of the ethanolic extract 

of T. diversifolia on keloid fibroblast cell proliferation 

and collagen accumulation was expressed by the IC50 

value using probit regression analysis. The percentage of 

inhibition of keloid fibroblast proliferation increases 

gradually with the given dose extract of T. diversifolia 
with a very strong correlation (r = 0.838; p = 0.000 in 72 

hours; r = 0.924; p = 0.000 in 120 hours of incubation) 

with the lowest IC50 value of 3.624 μgmL
-1 at an 

incubation time of 120 hours (Wahyuningsih et al., 

2015). Furthermore, Ranti et al, in 2018 tested the 

cytotoxic activity of tagitinin C on keloid fibroblast cells 

with IC50 values of 0.122 μgmL
-1 (72 hours incubation) 

and 0.039 μgmL-1 (120 hours) which affected the 

deposition of 53.1% of keloid collagen (72 hours) and 

44.3% (120h). The selectivity index of tagitinin C in 

normal fibroblasts (NF) was 287 (72 hours incubation) 

and 791 for (120 hours incubation). Based on these 

results, it was concluded that the ability of tagitinin C to 

inhibit keloid fibrosis viability and reduce keloid 

collagen deposition was consistent with the 

concentration and incubation time. The process of 

collagen synthesis happened when the fibroblast got a 

stimulus from TGF-β that was bound to TGF-β receptors 

on the fibroblasts membrane. When an injury occured, 

the TGF-β will be separated from the binding protein 

give respond to mechanical trauma system. However, 

there have not been many studies on the inhibitory 

activity of TGF-β by T. diversifolia compound.  But, 

another study have found that the sesquiterpene lactones 

is known to inhibit the keloid fibroblasts proliferation, 

inhibit TGF-β1, and inhibit collagen synthesis of keloid 

through the NF-κB (Ranti et al., 2018). 

The next study was carried out by Wahyuningsih, et 

al in 2019 to determine the antifibrocytic mechanism of 

T. diversifolia extract. The study showed that the 

ethanolic extract of T. diversifolia at concentrations of 

20 gmL-1, 10 gmL-1, and 5 gmL-1 for 24 hours in keloid 

fibroblast culture showed slower migration activity 

compared to untreated keloid fibroblast culture (p<0, 

05). The study also showed that the expression of TGF-

β1 and VEGF in the treatment group given the ethanolic 

extract of T. diversifolia was significantly lower than 
untreated keloid fibroblasts (p<0.05). From those result, 

it can be concluded that the ethanolic extract of T. 

diversifolia can inhibit fibroblast migration activity and 
reduce the expression of VEGF and TGF-β1 in keloid 

fibroblasts. This mechanism further strengthens that T. 
diversifolia has great potential to be used as a keloid 

therapy (Wahyuningsih et al., 2019). 

Traditionally, T. diversifolia have been used to treat 
chronic hepatitis and liver diseases in Chinese herbal 

medicine. Further researh must be done to explore 

whether T. diversifolia can be used to treat hepatoma. 
(Lu et al., 2017). The study of the cytotoxic activity of 

the methanol extract of the leaves of T. diversifolia and 
tagitinin C against human hepatoma cells (Hep-G2) 

showed positive results.  The test results with the MTT 

assay showed IC50 values 40.0 ± 2.0 and 2.0 ± 0.1 

μgmL-1. This compound induces an increase population 

in the sub-G1, exhibited S phase arrest and results in the 

activation of caspase 3 and caspase 8 which confirms the 

data that the antiproliferative effect of this compound is 

through caspase-dependent apoptotic activity. Tagitinin 

C caused membrane blebbing, cell shrinkage, nuclear 

fragmentation, and chromatin condensation in hepatoma 

cells. Caspases, have an essential role in the regulation 

and the execution of apoptotic cell death. Caspase 3 well 

known as a key effector caspase in the apoptosis 

pathway, amplifying the signal from initiator caspases 

(such as caspase 8). This study show that tagitinin C 

induced apoptosis done by the activation of the caspase 

cascade (Liao at al., 2012). A follow-up study was 

conducted by Lu in 2017 to showed another cytotoxic 

effect of T. diversifolia on Hep G2 cells. The results of 

the study showed that the induction of apoptosis such as 

DNA fragmentation could increase the level of apoptosis 

and apoptosis of the sub-G1 population in the treatment 

group that given the acetate extract leaves of T. 



 

 

 

90 Biology, Medicine, & Natural Product Chemistry 10 (2), 2021: 87-91 
 

 

diversifolia. In addition, the acetate extract of the leaves 
of T. diversifolia was also increase the expression of the 

proapoptotic protein Bax Bcl-2. Based on this study, it 

prove the cytotoxicity induced by ethyl acetate extracts 

of T. diversifolia leaves (Td-L-EA) in human HepG2 

hepatoma cells that strengthen ethnopharmocologic use 

of T. diversifolia (Lu at., 2017). 

The cytotoxic effect of T. diversifolia leaf extract on 
RAW264.7 cells and human mononuclear peripheral 

blood cells (PBMC) by mitochondrial respiration 

method was also studied. The results of the study 

showed that the IC50 concentration in PBMC 

proliferation was 4.42 μgmL-1 and in RAW264.7 cells 

the IC50 value was 11.63 μgmL
-1. The study 

demonstrated an immunomodulating effect by the leaf 

extract of T. diversifolia, which was produced the 

inhibition of phytohemagglutinin-M-induced PBMC 

proliferation and LPS-induced nitric oxide production in 

RAW264.7 macrophages. The hydrogen peroxide are 

able to induce cell death under stress conditions through 

apoptosis, but the anti-oxidant compound can protect 

this condition. The data showed that T. diversifolia 
aqueous extract showed an anti-oxidative capacity 

equivalent of (241.04 ± 11.93 mmol Troloxg-1) from 

ABTS assay and (94.89 ± 2.69 mmol Troloxg-1) from 

DPPH assay, respectively. The anti-oxidative capacity 

of T. diversifolia aqueous extract was equivalent to 
(32.62 ± 1.87) and (20.99 ± 2.79) mg NACg-1 in the 

ABTS and DPPH assays, when NAC was used as the 

standard compound. However, the calculated 

concentration was out of the non-cytotoxic range, which 

should be lower than 30 mg/mL. Thus, this calculated 

concentration based on the antioxidant capacity could 

not be used in practice in the hydrogen peroxide-induced 

cell death model.  

 It could be conclude that the effects of the 

immunomodulation caused by the aqueous extract from 

T. diversifolia. The mechanism can desccribe such as 
anti-PHA-M-induced PBMCs proliferation and antiLPS-

induced nitric oxide production from macrophages in the 

range of non-cytotoxic concentrations (Hiransai et al., 

2016). 

 

 

CONCLUSION 
 

Based on the literature study, it is found that some 

isolate from the extract of Tithonia diversifolia 
(Hemsley) A. Gray) have the anticancer activity in 

several different types of cancer cells. The active 

substances contained in the leaves of the T. diversifolia. 
The compound material which has been known to 

become an anticancer alternative therapy is tagitinin C. 

The extract of the leaves T. diversifolia has several 
anticancer mechanisms related to antifibrotic activity 

and the induction of apoptosis. Further research can be 

develop to find out another potential compound from the 

T. diversifolia extract. We hope there will be a new 
chance to find better alternative therapy for cancer.  

 

Conflict of interest: The author declares that there are 

no conflicts of interest concerning the publication of this 

article.  

 
 
REFERENCES 
 
Aryan, H. 2018. The Role of Herbal Medicine as Anti-Cancer 

Medicine: From Claim to Truth. Golden Medical Journal, 

7:e1179. DOI: 10.22086/gmj.v0i0.1179 

American Cancer Society. 2021.Basis Cancer. 

https://www.cancer.org/cancer/cancer-basics.html 

Babazadeh, A., Zeinali, M., Hamishehkar, H. 2018. Nano-

Phytosome: A Developing Platform for Herbal Anti-Cancer 

Agents in Cancer Therapy. Bentham Science. 19: 170-180. 

10.2174/1389450118666170508095250 

Farias, A., Rodrigues, A., Martins, R., Rabelo, E., Farias, C., de 

Almeida, S. 2019. Chemical Characterization, Antioxidant, 

Cytotoxic and Microbiological Activities of the Essential Oil 

of Leaf of Tithonia Diversifolia (Hemsl) A. Gray 

(Asteraceae). Pharmaceutical. 12, 34; 

doi:10.3390/ph12010034 

Gabule Ang, A., Enot, M., Baltazar, G., Alinapon, C., Buncales, 

E., Barbosa, G. 2019. Antioxidant and Cytotoxic Activity of 

the Leaf Ethanolic Extracts of Tithonia diversofilia and 

Gliricidia sepium from Bukidnon, Philippines. Asian Journal 

of Biological and Life Science. 8(1): 8-15. DOI: 

10.5530/ajbls.2019.8.2  

Gu, J., Gills, J., Park, E., Greenwood, E., Hawthorne, M., 

Axelrod, F., Chavez, P., Fong, H., Mehta, R., Pezzuto, J., 

Kinghorn, A. 2002. Sesquiterpenoids from Tithonia 

diversifolia with Potential Cancer Chemopreventive Activity. 

Journal Natural Products. 65: 532-536. 

Hausman, D. 2019. What is Cancer?. Perspective in Biology and 

Medicine, 6(4): 778-784. DOI: 

https://doi.org/10.1353/pbm.2019.0046.  

Hiransai, P., Tangpong, J., Kumbuar, C., Hoonheang, N., 

Rodpech, O., Sangsuk, P., Kajklangdon, U., Inkaow, W. 

2016. Anti-nitric oxide production, anti-proliferation and 

antioxidant effects of the aqueous extract from Tithonia 

diversifolia. Asian Pacific Journal of Tropical Biomedicine. 

6(11): 950–956. http://dx.doi.org/10.1016/j.apjtb.2016.02.002. 

Infodatin. 2019. Beban Kanker di Indonesia. Kementrian 

Kesehatan Republik 

Indonesia.https://pusdatin.kemkes.go.id/download.php?file=d

ownload/pusdatin/infodatin/Infodatin-Kanker-2019.pdf 

Lee, M., Liao, M., Tsai, Y., Chiu, K., Wen, H. 2011. 

Identification and Anti-Human Glioblastoma Activity of 

Tagitinin C from Tithonia diversifolia Methanolic Extract. 

Journal of Agricultural and Food Chemistry. 59:2347-2355. 

dx.doi.org/10.1021/jf105003n 

Liao, M., Tsai, Y., Yang, C., Juang, C., Lee, M., Chang, L., Wen, 

H. 2012. Anti-human hepatoma Hep-G2 proliferative, 

apoptotic, and antimutagenic activity of tagitinin C from 

Tithonia diversifolia leaves. Journal Natural Medicine. DOI 

10.1007/s11418-012-0652-0 

Lu, M., Huang, H., Chiou, W., Huang, R. 2017. Induction of 

Apoptosis by Tithonia diversifolia in Human Hepatoma Cells. 



 

 

 

 Rizkawati – Potential of Tithonia diversifolia as Anti-Cancer Agents 91 
 

 

Pharmacognosy Magazine.; 13:702-706. DOI: 10.4103/0973-

1296.218113. 

Miranda, M., Varela, R., Torres, A., Molinillo, J., Gualtieri, S., 

Macias, F. 2015. Phytotoxins from Tithonia diversifolia. 

Journal Natural Products. DOI: 

10.1021/acs.jnatprod.5b00040 

Ranti, I., Wahyuningsih, M., Wirohadidjojo. 2018. The 

antifibrotic effect of isolate tagitinin C from tithonia 

diversifolia (Hemsley) A. Gray on keloid fibroblast cell. Pan 

African Medical Journal. 30:264. 

doi:10.11604/pamj.2018.30.264.9994 

Tagne, A., Marino, F., Cosentino, M.2018. Tithonia diversifolia 

(Hemsl.) A. Gray as a medicinal plant: A comprehensive 

review of its ethnopharmacology, phytochemistry, 

pharmacotoxicology and clinical relevance. Journal of 

Ethnopharmacology. 220: 94-116. 

https://doi.org/10.1016/j.jep.2018.03.025 

Wahyuningsih, M., Syarif, R., Suharmi, S., Murini, T., Saputra, 

F., Suryo, A. 2013. Selectivity Of Purified Extract From The 

Leaves Of Tithonia Diversifolia (Hemsley) A.Gray) Against 

Hela Cells. Traditional Medicine Journal. Vol. 18(1), p 22-

28.  

Wahyuningsih, M., Wirohadidjojo, Y., Hidayat, R., Sadid, A. 

2015. Antifibrotic Effect of Standardized Ethanol Extract of 

Tithonia diversifolia (Hemsley) A. Gray on Keloid 

Fibroblasts. International Journal of Pharmacognosy and 

Phytochemical Research. 7(4); 642-647.  

Wahyuningsih, M., Nugrahaningsih, D., Budiyanto, A.2019. 

Ethanolic Extract of Tithonia Diversifolia (Hemsley) A. Gray 

Inhibits Migration Activity and Decrease the Transforming 

Growth Factor-Beta1, Vegf Expression On Keloid 

Fibroblasts. Asian Journal of Pharmaceutical and Clinical 

Research. 12(1): 342-345. DOI: 

http://dx.doi.org/10.22159/ajpcr.2019.v12i1.29850 

World Health Organization, 2021. Cancer. 

https://www.who.int/health-topics/cancer#tab=tab_1 

 

 



 

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