INTRODUCTION:

Cancer remains the second leading cause of mortality worldwide and continues to increase at an estimated rate of 12% annually ^1–3. Despite advances in conventional therapies, there is still an urgent need to identify safer and more effective treatment alternatives. In recent years, complementary and alternative medicine has gained attention as a promising approach in cancer management ⁴. Natural products and their derivatives have long been recognized as valuable sources of chemotherapeutic agents, with approximately 61% of anticancer drugs originating from natural compounds or their structural analogues ⁵.

The red palm (Cyrtostachys renda), a member of the Arecaceae family, has traditionally been used as an ornamental plant for medicinal purposes in several Asian countries, including India, China, and Australia ⁶. Secondary metabolites from this family, such as arecoline, procyanidins, luteolin, and catechins, have been reported to exert anticancer effects, primarily by inducing apoptosis in cancer cells such as Hep-2 and HeLa ^7,8. Phytochemical analysis of C. renda extracts has revealed the presence of alkaloids, flavonoids, saponins, tannins, steroids, and terpenoids ⁹. Previous studies have also shown cytotoxic activity in fruit and root extracts, as evidenced by the brine shrimp lethality test (LC₅₀ values ranging from 43.42 ± 0.66 to 285.19 ± 0.58 μg/mL) ^9,10, and the antiproliferative effects of several solvent extracts against MCF-7, T47D, and HeLa cells, with indications that these extracts could enhance the cytotoxicity of doxorubicin ^9,11.

Based on this evidence, the present study was conducted to evaluate the cytotoxic and selective activities of four fractions (C, E, K, and O) of Cyrtostachys renda against human cancer cell lines (HeLa, MCF-7, and T47D), using Vero cells as a non-cancer control. Among these, fraction O exhibited the lowest IC₅₀ value against HeLa cells, reflected the most potent antiproliferative activity, and showed a favorable selectivity index; thus, this fraction was selected for further investigation. To explore its therapeutic potential, fraction O was subsequently tested in combination with doxorubicin in HeLa cells, and its mechanism of action was examined using flow cytometry to assess apoptosis induction and cell cycle arrest. These findings are expected to provide new insights into the potential application of C. renda, particularly fraction O, as a promising natural adjuvant for cancer therapy.

MATERIAL AND METHODS:

Plant Materials:

Cyrtostachys renda was harvested in Muaro Jambi regency, Jambi Province, and identified in Jatinangor Herbarium, Plant Taxonomy Laboratory, Department of Biology, Faculty of Mathematics and Natural Sciences, Padjadjaran University, with herbarium voucher number 48/HB/04/2022.

Plant Fractions Extraction:

The methanol extract was prepared by grinding a dried sample of C. renda fruit, then mixing the powder with methanol in a 1:20 (w/v) ratio. The sample was macerated three times to dissolve the solvent into a clear liquid, and every maceration procedure was carried out for 24 hours. The solvent was eliminated using a rotary evaporator to create a crude methanol extract. Then, it was partitioned into n-hexane: methanol (1:1) and proceeded with other solvents, dichloromethane and ethyl acetate.

Fractionation using Vacuum Liquid Chromatography (VLC):

This technique uses a series of solvents with different polarities, such as those used in TLC, as the mobile phase. The stationary phase is silica gel 60 with a 70-230 mesh size. A combination of n-hexane, ethyl acetate, and methanol is an eluent system used in the fractionation process. The solvents' polarity increases from non-polar to polar. The filtrate is collected in a porcelain container and allowed to air dry after the solvent is continuously poured during a vacuum procedure. Every resultant fraction is then weighted.

Fractionation using Gravity Column Chromatography (GCC):

20 g of silica gel G60 was put within the GCC, 2 g of the sample dissolved in n-hexane, and 4 g of silica gel G60 was spread out on top of the GCC. The mixture was swirled until it dried (impregnation) and blended until it was equally distributed. The elution procedure was then completed by adhering to the eluent sequence specified in Table 1. Selected eluents were poured into the column to complete the elution process. The eluent from the column was placed in a container for storage. This process was repeated until the most polar eluent was obtained, and the eluent's polarity increased gradually. The TLC results of each fraction were examined using UV light and the dye Von’s reagent, and the same Rf (Retardation factor) values were combined and concentrated.

Determination of Cytotoxic Activity and Selectivity Index:

The cytotoxic activity of fractions C, E, K, and O of Cyrtostachys renda was evaluated against HeLa, MCF-7, and T47D cancer cell lines, with Vero cells as a non-cancer control, using a modified MTT assay protocol adapted from Shanti et al. ¹². Cells were seeded at a density of 1 × 10⁴ cells/well in 96-well plates and incubated for 24 h at 37°C in a humidified atmosphere containing 5% CO₂. The test samples were dissolved in culture media using DMSO as a cosolvent, ensuring a final concentration of less than 0.1% (v/v). After 24 h of incubation with various concentrations of test fractions (15.6–500 µg/mL), the media were discarded, and the cells were washed with phosphate-buffered saline (PBS). Subsequently, 0.5 mg/mL MTT solution in PBS was added, and the plates were incubated for 4 hours at 37°C. The formazan crystals formed were dissolved overnight using 10% sodium dodecyl sulfate (SDS) in 0.01 N HCl. Absorbance was measured at 595 nm using a microplate reader, and the IC₅₀ value was calculated from the dose-response curve.

The Selectivity Index (SI) was determined by comparing the IC₅₀value in Vero cells with the IC₅₀ value in each cancer cell line, calculated as:

IC50 (Vero Cells)

SI= -------------------------------

IC50(Cancer Cells)

Higher SI values indicate greater selectivity toward cancer cells relative to normal cells.

Determination of the Combination Cytotoxicity and the Combination Index:

Fraction O, identified as the most cytotoxic fraction based on the lowest IC₅₀ value against HeLa cells, was further tested with doxorubicin. HeLa cells were treated with serial concentrations of doxorubicin (1.4, 2.8, and 5.6 µg/mL) and fraction O (14, 28, and 56 µg/mL), either alone or in combination. Cell viability was assessed using the MTT assay described above.

The interaction between fraction O and doxorubicin was evaluated using the Combination Index (IC) method according to the Chou–Talalay equation:

D₁ D₂

CI= ---------- + ---------

D_x1D_x2

D1 and D2 are the combined concentrations of O-fraction and doxorubicin required to achieve a specific effect, and Dx1 and Dx2 are the concentrations of each agent separately needed to achieve the same effect. IC values were interpreted as follows: IC < 1 indicates synergism, IC = 1 indicates an additive effect, and IC > 1 indicates antagonism.

Cell Imaging:

Following the application of fraction O and doxorubicin, the morphological changes of the cells were evaluated and documented using a phase contrast microscope.

Flow Cytometry Evaluation of Apoptosis and Cell Cycle Modulation:

Flow cytometry was used for cell cycle and apoptosis analysis, and the working procedure was referred to Utami et al. ¹³. Propidium iodide (PI) staining was used to assess the cell cycle, and an Annexin-FLUOS/PI staining kit following the protocol kit (Roche, Basel, Switzerland) was used to determine apoptosis.

Statistical Analysis:

The SD (standard deviation) and mean were used to express all data. To evaluate statistically significant differences with a p<0.05 criterion, the Student's t-test was utilized.

RESULT:

C. renda Bioactive Fractions:

Table 1 shows that secondary metabolites were found in fraction C, which showed terpenoid, fraction E contained phenolic and tannin, fraction K contained flavonoid, and fraction O contained phenolic and flavonoid.

Cytotoxic Effect of C. renda Bioactive Fractions:

The effects of C. renda fruit fractions on the viability of MCF-7 and T47D breast cancer cells, HeLa cervical cancer cells, and Vero normal kidney cells were studied. After incubation of cells with each fraction for 24 h, viable cells were measured by MTT assay. At a 112 μg/mL concentration, fraction O inhibited the growth of HeLa cells by 50%; no cytotoxicity was observed on Vero cells. Table 2 shows that fraction O had modest cytotoxic effects and a selective action selectivity index.

Cytotoxic Effect of C. renda Bioactive Fractions in Combination:

In this study, the effect of HeLa cell treatment with a combination of fraction O at concentrations of 14, 28, and 56 µg/mL and doxorubicin at concentrations of 1.4, 2.8, and 5.6 µg/mL for 24 hours resulted in 53–70% inhibition of cell growth (Table 3) in a dose-dependent manner.

The morphology of living and dead HeLa cells (a human cervical cancer cell line) can be distinguished under a microscope based on several key features. These differences arise due to changes in cell structure, membrane integrity, and overall cell shape, which occur when cells are healthy or undergo apoptosis, necrosis, or autophagy (Fig. 3).

DISCUSSION:

Natural products are widely recognized for their ability to treat illnesses, including cancer. Information about bioactive substances and their biological effects is currently limited because C. renda plants primarily serve as ornamental plants for everyone, with limited use as therapeutic herbs. Because of the antioxidant and anticancer properties of C. renda substances, previous studies have indicated that the plant includes intriguing secondary metabolites that might be used as cancer chemoprevention or a therapeutic complement. The study examined the anticancer effects of four fractions (C, E, K, and O) separated from C. renda. The best results were then further analyzed to determine the synergistic effect of the combination therapy with the chemotherapeutic drug doxorubicin. The fraction's ability to induce apoptosis and cell cycle arrest, and its proliferative activity, were also assessed.

Based on an analysis of previous studies, n-hexane, dichloromethane, ethyl acetate, and methanol extracts from the fruits and roots of C. renda presented potent antiproliferative capability against several types of cell lines and their fractions ^10,11. For the first time, the antiproliferative properties of this plant were investigated. Compared to fractions C, E, and K, fraction O extracted from C. renda fruits was more active in this study. According to this assay, the molecule obtained from the ethyl acetate fraction is more active. The separation results showed that fraction O contained flavonoid and phenolic fractions based on the results of the spray reaction identification (Table 1). This may suggest that the semi-polar causes the antiproliferative action in this plant to the polar active principle. These results follow previous studies that reported that semi-polar to polar fractions, such as phenolic and flavonoid groups, have potential antiproliferative activity ^14,15. Due to multiple studies on C. renda, no information is currently accessible about the separation of bioactive chemicals and their anticancer activity analysis. This study further isolated and identified the active components in C. renda.

According to Prayong et al, the cytotoxic activity criteria of metabolites with IC₅₀ values > 100 μg/mL are in the moderate category. Fraction O shows the highest antiproliferative potential among the other three fractions, with an IC₅₀ value of 112 μg/mL (Table 2), which is included in the moderate criteria. Fraction O shows moderate preference/selectivity towards cancer cells compared to normal cells, so it is considered to have anticancer potential that needs to be studied further. Fractions C, E, K, and O showed different activities on various cell lines; for example, fraction O IC₅₀ value against HeLa cells was 112 μg/mL, whereas 217 μg/mL on MCF-7. This selectivity could be caused by tissue-specific responses or the cell lines' sensitivity to the active fractions in the sample. Previous studies have reported that the phenolic and flavonoid fractions have antiproliferative activity from low to potent cytotoxic and non-selective to very selective ^16,17. Cancer cells' diverse responses to exposure to anticancer bioactive fractions arise due to genetic, epigenetic, and microenvironmental factors and differences in drug metabolism and drug resistance mechanisms ^18,19.

The combination of doxorubicin with natural fractions from the phenolic and flavonoid groups has been explored in cancer research, and several studies have shown that the combination can enhance the cytotoxic effect of doxorubicin against several types of cancer cells ^20,21. The synergistic effect observed in the combination can also increase the efficacy of doxorubicin while potentially reducing its side effects ^22,23. The combination of doxorubicin with natural fractions from the phenolic and flavonoid groups has been explored in cancer research, and several studies have shown that the combination can enhance the cytotoxic effect of doxorubicin against several types of cancer cells, including MCF-7, T47D, and HeLa cancer cells ^11,22. The synergistic effect observed in the combination with phenolic and flavonoid might also increase the efficacy of doxorubicin while potentially reducing its side effects ^24,25. The results of the cytotoxic test of the combination of fraction O and doxorubicin with variations in sub-IC₅₀ concentrations showed inhibition of HeLa cell growth of more than 50% (Table 3), with a CI score of 0.2 to 0.6, which means it provides a strong synergistic effect (Table 4). The combination of fraction O 28 mg/mL and doxorubicin 2.8 mg/mL inhibited HeLa cell growth by up to 58.01% with a CI score of 0.3 (strong synergistic) (Table 4). These results are consistent with previous research reports that the cytotoxic effect of doxorubicin can be enhanced and the side effects of doxorubicin can also be suppressed by combining it with natural fractions from the phenolic and flavonoid groups, such as quercetin, EGCG, curcumin, and resveratrol ^26-28.

Numerous cytotoxic medications act by initiating cell cycle arrest and apoptosis in cancer cells. The cell cycle regulates cancer cell proliferation. Apoptosis, DNA damage repair, or cell cycle arrest can result from the activation of specific checkpoints by these cytotoxic substances, which cause DNA damage ²⁹. Phenolic fractions and flavonoids have induced cell cycle arrest at the G0/G1 phase, S phase, and G2/M phase ^30,31. In this study, the cell cycle progression was evaluated to determine when the bioactive fractions of C. renda could inhibit HeLa cell growth by inducing cell cycle arrest. The results showed fraction O caused HeLa cell growth to stop at the G1 and G2/M phases (Figure 1A and 1B). Fraction O also caused a sub-G1 peak (Figure 1A), indicating the occurrence of apoptosis, characterized by an increase in the content of fragmented DNA (sub-diploid) ³². The occurrence of cell cycle arrest in this study was due to the role of polyphenols, which are phenolic and flavonoid fractions contained in fraction O. Previous studies have reported that phenolic and flavonoid fractions can cause G2/M phase cell cycle arrest through several mechanisms, including induction of DNA damage, inhibition of cyclin-dependent kinases (CDKs), activation of checkpoint kinases, and modulation of oxidative stress ^33,34. This suggests that the fraction may repress oncogene transcription factors or trigger tumor suppressor genes, and it may also function as an antimitotic agent, much as acridine fraction ³⁵. The types of phenolic fractions that exert their effects on G2/M arrest include resveratrol and curcumin, which activate the p53 pathway, increase p21 expression, inhibit CDK1/cyclin B activity, and disrupt microtubule dynamics ³⁶. Several flavonoid fractions have been shown to cause G2/M phase cell cycle arrest in cancer cells effectively. The primary mechanisms include inhibiting key cell cycle regulators like CDK1/cyclin B, induction of oxidative stress and DNA damage, and activation of tumor suppressor proteins like p53 and p21. Other proteins involved in the signaling pathway in cervical cancer include Wnt/β-catenin, ERK/MAPK, and PI3K/Akt ³⁷. The ability to induce cell cycle arrest may be beneficial in cancer therapy, as it may prevent cancer cells from dividing, ultimately leading to death. However, the exact effects of these fractions may vary depending on the specific phenolic and flavonoid fractions, their concentration, and the type of cancer cells involved. Therefore, although phenolic and flavonoid fractions may hold promise in cancer therapy, further research is needed to understand their therapeutic potential as cell cycle modulators and how they may be integrated into cancer treatment strategies.

Apoptosis is a process of programmed cell death that is crucial for preserving homeostasis in the body. Proapoptotic protein expression will be low, and antiapoptotic protein expression will be high when body homeostasis is disrupted, as cancer's apoptosis pathway is often dysregulated. As a result, most anticancer medications cause cell death by focusing on the extended apoptosis pathway ³⁸. Membrane clumping, nuclear fragmentation, chromatin condensation, externalization of phosphatidylserine in the cytoplasmic membrane, apoptotic body formation, and decreased cell volume are all characteristics of cells going through apoptosis ³⁹. Biochemical studies on HeLa cells were conducted to evaluate apoptosis due to fraction O. Phosphatidylserine is a biochemical indicator of apoptosis ⁴⁰. The results of this study showed that administration of fraction O caused increased apoptosis in the early (annexin+/PI-) and late (annexin+/PI+) apoptosis up to 20.3% when compared to control cells (untreated) (Figure 2A). Similar results were also found in the fraction O 28 μg/mL combined with doxorubicin 2.8 μg/mL, where apoptosis increased up to 19.1% compared to control cells but was accompanied by increased cell necrosis. Increased cell death due to necrosis or outside the apoptosis pathway was due to the effect of treatment with doxorubicin. This was observed in the group of cells treated with a single dose of doxorubicin, which showed 65.8% necrosis (Figure 2B). Previous studies reported that doxorubicin had side effects, causing cell damage and death outside the apoptosis signal transduction pathway ⁴¹. In the majority of cancer cells, doxorubicin acts by inducing apoptosis. However, when cells are under a lot of stress, the extent of the damage and the lack of apoptosis or repair processes might cause necrosis ⁴².

Induced cancer cell death through necrosis can be beneficial and detrimental in cancer therapy, depending on the specific context. Necrosis can destroy cancer cells and stimulate the immune system under advantageous situations, enhancing the therapeutic effect ⁴³. In harmful contexts, necrosis can cause inflammation, tissue damage, and potential tumor progression that complicates treatment ⁴⁴. Controlled cancer cell necrosis is usually not the primary goal in cancer therapy. In most cases, apoptosis is preferred, as it is a more orderly and clean process that minimizes damage to surrounding normal tissue. However, in certain circumstances (e.g., in poorly vascularized tumors or hypoxic areas), inducing necrosis may be a side effect of treatment, and its effects can be strategically exploited. Therefore, minimizing harmful necrosis while promoting apoptotic mechanisms is essential in developing effective cancer therapies. Further research is needed to better understand how necrosis can be safely induced and controlled in cancer therapy.

Healthy, living HeLa cells are round or elongated, depending on the cell culture conditions. Viable HeLa cells maintain a healthy, well-defined morphology with intact membranes and functioning organelles⁴⁵. Apoptotic HeLa cells show controlled shrinkage, chromatin condensation, and membrane clumping, ultimately leading to cell fragmentation ⁴⁶. Necrotic HeLa cells show cell swelling, organelle disintegration, and membrane rupture, which leads to inflammation ⁴⁷. Autophagic HeLa cells show vacuolization and the presence of autophagic vesicles, with some morphological changes, but not as severe as necrosis ⁴⁸. Light, fluorescence, or electron microscopy techniques can observe these morphological changes. They can distinguish between live and dead cells or different forms of cell death in HeLa cultures.

According to the morphological traits of the cells above, this study's observations show morphological changes between control cells and groups of cells treated with fraction O, doxorubicin, and a combination of fraction O with doxorubicin (Figure 3). The three groups of treated cells experienced apoptosis with characteristics shown in controlled shrinkage, chromatin condensation, and membrane clumping, which eventually caused cell fragmentation. Meanwhile, control cells showed healthy cell conditions with attributes of a rounded or elongated shape, homogeneous and precise cytoplasm, attached and dense cells with a spreading morphology, especially during confluence. Further observation with cell staining needs to be done so that cell organelles can be observed, such as the distribution of chromatin threads that are evenly distributed or can appear as a smooth and loose structure, and the center of the cell contains the nucleus. The cell membrane is undamaged and appears soft and unhindered.

CONCLUSION:

This study revealed that fraction O has the most potent cytotoxic activity compared to fractions C, E, and K. Fraction O shows a fraction profile containing more than one group of secondary metabolites based on the results of TLC and color reactions. Phenolic and flavonoid fractions are metabolites responsible for the expressed biological activity. The results of this study revealed that fraction O has the most potent single cytotoxic activity (IC₅₀ 112 µg/mL) compared to fractions C, E, and K. Metabolite also showed a selective cytotoxic profile against HeLa cancer cells compared to normal Vero cells. Although fraction O has not shown a pure fraction profile based on TLC results and color reactions, the fraction groups that make it up can be identified, including phenolics and flavonoids, which are metabolites responsible for the expressed biological activity. When fraction O (28 mg/mL) was applied with doxorubicin (2.8 mg/mL), it also showed antiproliferative activity against HeLa cells with a strong selective category. It induces cell cycle arrest in the G1 and G2/M phases and might induce apoptosis.

CONFLICT OF INTEREST:

The authors declare no conflicts of interest in this paper.

ACKNOWLEDGMENTS:

We would like to thank Prof. Taifo Mahmud for supporting the research facilities in separating the crude extract of C. renda fruit. We also thank Ria Novia, Sarah Dianora S., Amalia Rani, and Mira Ovita D. for helping prepare plant material for this research. This research was funded by the Institute for Research and Community Service, University of Jambi, Indonesia [award number: 2213/UN21.11/PT.01.05/SPK/2023].

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Received on 08.05.2025 Revised on 06.09.2025

Accepted on 01.11.2025 Published on 20.05.2026

Available online from May 25, 2026

Research J. Pharmacy and Technology. 2026;19(5):2310-2318.

DOI: 10.52711/0974-360X.2026.00332

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

Sample code	Fraction group	Before spraying the Von’s reagent		After spraying the Von’s reagent		Result^*
Sample code	Fraction group	Visible light	UV 366 nm	Visible light	UV 366 nm	Result^*
Fraction C	Terpenoid	Colorless	Light blue	Light Purple	Purple	+
Fraction E	Phenolic	Light green	Purplish red	Black	Grey	+
Fraction E	Tannin	Light green	Purplish red	Black	Black	+
Fraction K	Flavonoid	Light green	Faded red	Brown	Blackish yellow	+
Fraction O	Phenolic	Light green	Faded red	Black	Grey	+
Fraction O	Flavonoid	Light green	Faded red	Brown	Blackish yellow	+

Sample code	IC₅₀ (µg/mL)^*				Selectivity Index (SI)^**
Sample code	HeLa	MCF-7	T47D	Vero	HeLa	MCF-7	T47D
Fraction C	1660.42±4.29	409.79±5.05	9962.50±2.78	1190.09±0.62	0.72	2.90	0.12
Fraction E	783.10±2.26	748.77±3.19	1978.77±2.07	779.44±0.36	1.00	1.04	0.39
Fraction K	338.22±3.49	221.55±3.04	586.50±3.12	518.04±0.44	1.53	2.34	0.88
Fraction O	112.38±2.75	217.14±4.51	635.16±2.16	864.98±0.41	7.70	3.98	1.36
Doxorubicin^a	11.47±3.11	4.59±2.14	0.55±1.98	19.78±2.65	1.72	4.31	35.96

Concentration of Fraction O (µg/mL)	Cell Viability (%)
Concentration of Fraction O (µg/mL)	0	1.4	2.8	5.6
0	100.00±0.00	91.86±2.15	87.75±0.56	82.76±0.31
14	86.71±0.31	47.52±0.74	48.41±0.29	38.95±1.48
28	81.72±1.74	46.93±0.12	41.99±0.56	35.63±0.52
56	66.20±1.89	37.09±2.49	37.91±2.38	30.35±1.49

Syamsurizal¹*, Diah Tri Utami¹, Sutrisno²

MATERIAL AND METHODS:

Plant Materials:

Plant Fractions Extraction:

Fractionation using Vacuum Liquid Chromatography (VLC):

Fractionation using Gravity Column Chromatography (GCC):

Determination of Cytotoxic Activity and Selectivity Index:

Determination of the Combination Cytotoxicity and the Combination Index:

The interaction between fraction O and doxorubicin was evaluated using the Combination Index (IC) method according to the Chou–Talalay equation:

Cell Imaging:

Flow Cytometry Evaluation of Apoptosis and Cell Cycle Modulation:

Statistical Analysis:

RESULT:

Cytotoxic Effect of C. renda Bioactive Fractions:

Cytotoxic Effect of C. renda Bioactive Fractions in Combination:

Regulation of the Cell Cycle Effects of Fraction O with Doxorubicin:

The Effect of Fraction O and Doxorubicin on Apoptosis in Cells:

DISCUSSION:

CONCLUSION:

CONFLICT OF INTEREST:

ACKNOWLEDGMENTS:

REFERENCES:

Concentration of Fraction O (µg/mL)	Combination Index (CI)^*
Concentration of Fraction O (µg/mL)	1.4	2.8	5.6
14	0.2	0.3	0.3
28	0.3	0.3	0.4
56	0.5	0.5	0.6

Syamsurizal1*, Diah Tri Utami1, Sutrisno2

MATERIAL AND METHODS:

Plant Materials:

Plant Fractions Extraction:

Fractionation using Vacuum Liquid Chromatography (VLC):

Fractionation using Gravity Column Chromatography (GCC):

Determination of Cytotoxic Activity and Selectivity Index:

Determination of the Combination Cytotoxicity and the Combination Index:

The interaction between fraction O and doxorubicin was evaluated using the Combination Index (IC) method according to the Chou–Talalay equation:

Cell Imaging:

Flow Cytometry Evaluation of Apoptosis and Cell Cycle Modulation:

Statistical Analysis:

RESULT:

Cytotoxic Effect of C. renda Bioactive Fractions:

Cytotoxic Effect of C. renda Bioactive Fractions in Combination:

Regulation of the Cell Cycle Effects of Fraction O with Doxorubicin:

The Effect of Fraction O and Doxorubicin on Apoptosis in Cells:

DISCUSSION:

CONCLUSION:

CONFLICT OF INTEREST:

ACKNOWLEDGMENTS:

REFERENCES:

Syamsurizal¹*, Diah Tri Utami¹, Sutrisno²