Dinesh kumar*, Priyanka Tomar1
Research Associate, Central Leather Research Institute, Chennai
Show Author Information
Author Information: Dinesh Kumar, & Priyanka Tomar
Title: In vitro Investigation of Rhaphidophora decursiva Extract for the treatment of Lung Cancer
Journal: PEXACY International Journal of Pharmaceutical Science
Volume and Issue: Vol. 2, Number 8
Page Numbers: 113–131
Version: Version 1
Abstract: Lung cancer remains a leading cause of cancer-related mortality, underscoring the urgent need for innovative therapeutic strategies. This study investigates the anti-cancer properties of Rhaphidophora decursiva extracts (methanol and ethanol) on lung cancer cells in vitro. The research encompassed various assays including cytotoxicity, cell viability, colony formation suppression, and flow cytometry to ascertain the extracts’ efficacy. Significant inhibition of cell proliferation, colony formation, and cell cycle arrest at the G0/G1 phase were observed, highlighting the therapeutic potential of these extracts. The findings reveal Rhaphidophora decursiva as a promising natural remedy and provide a foundation for future in-depth investigations. This research represents a step towards harnessing the power of natural products in the fight against lung cancer.
Keywords: Lung cancer; Rhaphidophora decursiva; in vitro; cytotoxicity; cell viability; colony formation; cell cycle arrest; natural products; therapeutic potential.
Article can be accessed online on: PEXACY International Journal of Pharmaceutical Science
Corresponding Author- *diar6187@gmail.com
Update: Received on 20/08/2023; Accepted; 24/08/2023, Published on; 26/08/2023
INTRODUCTION
Lung cancer continues to be one of the most fatal malignancies worldwide, contributing to a significant proportion of cancer-related deaths [1]. Despite advances in medical science and the availability of several treatment modalities, the five-year survival rate for lung cancer remains disappointingly low [2]. This unsatisfactory prognosis can be attributed to late-stage diagnosis, metastasis, recurrence, and the development of resistance to conventional therapies [3].
In recent years, there has been a growing interest in exploring alternative therapeutic strategies, including the utilization of medicinal plants [4]. Many plants are rich in bioactive compounds that have shown promising anti-cancer effects. Their usage in traditional medicine, particularly in Asian countries, has often paved the way for modern scientific inquiry into their potential medical applications [5].
Rhaphidophora decursiva is one such plant. Belonging to the Araceae family, it is a lesser-known species that has been used in traditional medicine. However, its application in modern medicine, especially concerning lung cancer, remains largely unexplored [6]. Various compounds isolated from plants within the Araceae family have exhibited anti-inflammatory, antioxidant, and anti-cancer properties. Such evidence provides an intriguing foundation for a more detailed investigation of Rhaphidophora decursiva‘s potential efficacy against lung cancer [7].
This study aims to investigate the in vitro effects of Rhaphidophora decursiva extract on human lung cancer cells. Specifically, it will focus on evaluating the anti-proliferative, cytotoxic, and apoptotic-inducing properties of the extract. It will also explore the possible underlying molecular mechanisms that may be responsible for these observed effects [8].
By bridging the gap between traditional knowledge and modern scientific methods, this research hopes to contribute to the growing body of evidence supporting the use of medicinal plants in cancer treatment [9]. If successful, it may pave the way for developing a novel, natural, and more accessible therapeutic option for lung cancer patients, thereby potentially improving their prognosis and quality of life. The findings of this study could have broader implications in oncology, opening new avenues for the exploration of other plants and their extracts as potential cancer therapeutics [10].
In the following sections, the methodology will detail the extraction process, the cell lines used, and the various assays performed to assess the therapeutic potential of Rhaphidophora decursiva extract [11]. The results will provide a comprehensive analysis of the findings, followed by a discussion that will interpret these results in the context of current scientific understanding. Finally, the conclusion will summarize the key findings and suggest future directions for research in this exciting and important area of oncology [12].
Methodology
Collection of Plants [13]
Rhaphidophora decursiva, a plant from the Araceae family, was collected from a well-documented region known for its rich biodiversity. The plant was identified and authenticated by a botanist, and a voucher specimen was deposited in the herbarium for future reference. Following collection, the plant was thoroughly washed to remove any soil or debris and then allowed to air dry under controlled conditions. Once dried, the plant material was ground into a fine powder using a mechanical grinder, and the powdered material was carefully stored until further processing.
Extraction Process
Ethanol and Methanol Extraction [14]
For the extraction of phytochemicals from the powdered Rhaphidophora decursiva, both methanol and ethanol were chosen as solvents, owing to their varying polarities, which would allow for the extraction of a wide array of chemical constituents. The Soxhlet extraction method was employed, as it is known for its ability to provide complete extraction by maintaining an ideal temperature and utilizing a continuous solvent recycling process.
The powdered plant material was placed in a cellulose thimble, which was then positioned inside the Soxhlet apparatus. Both ethanol and methanol were used in separate extractions to ensure a broad recovery of phytochemicals. The solvents were heated to their respective boiling points, allowing for the vaporized solvent to travel up a distillation arm and condense over the plant material in the thimble. The condensed solvent then acted as a leaching agent, soaking into the plant material and dissolving the desired compounds
Phytochemical Analysis [15]
For the phytochemical analysis, the powdered plant material was subjected to solvent extraction using both ethanol and methanol in a specific ratio. This method was chosen to ensure that a wide range of phytochemicals, including both polar and non-polar compounds, could be extracted. The extracts were then evaporated under reduced pressure to yield a concentrated extract, which was carefully weighed and stored at a low temperature until required for analysis.
The concentrated extract underwent a series of comprehensive phytochemical screening tests. These tests were designed to identify the presence of various bioactive compounds such as alkaloids, flavonoids, tannins, saponins, and terpenoids. Each test was meticulously performed following standard procedures and observed by trained personnel.
Cytotoxicity Assay by MTT [16]
To evaluate the cytotoxic effects of Rhaphidophora decursiva extracts on lung cancer cells (A549), the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay was utilized. Cells were seeded in a 96-well plate at a density of 1×10^4 cells per well and treated with varying concentrations of the extract (50, 100, 200, and 400 µg/mL) dissolved in DMSO. After 24-hour incubation at 37°C, 5% CO2, 20 µl of MTT solution (5 mg/mL) was added to each well and incubated for 4 hours. The formazan crystals formed were dissolved in 150 µl of DMSO, and the absorbance was measured at 570 nm. The IC50 value, indicating the concentration required to inhibit 50% of the cell population, was determined.
Cell Viability Assay [17]
Cell viability was assessed using the Trypan Blue exclusion method. After treating the cells with various concentrations of the extract, they were stained with 0.4% Trypan Blue and counted under a microscope. Viable cells exclude the dye, while dead cells appear blue. This method helped in determining the effect of the extract on overall cell health and proliferation.
Colony Formation Assay [18]
To determine the ability of lung cancer cells to grow into colonies, cells were seeded at a low density (500 cells/well) in 6-well plates and treated with different concentrations of the extract (25, 50, and 100 µg/mL). After 14 days of incubation, colonies were fixed with methanol and stained with 0.5% crystal violet. Colonies containing more than 50 cells were counted and the plating efficiency and survival fraction were calculated to understand the effects of the extract on clonogenic survival.
Flow Cytometry [19]
Flow cytometric analysis was performed to study cell cycle progression and apoptosis. Cells were treated with selected doses of the extract (50, 100, and 200 µg/mL) and harvested by trypsinization. For cell cycle analysis, cells were fixed in 70% ethanol and stained with propidium iodide (PI), followed by analysis on a flow cytometer. The distribution of cells in G0/G1, S, and G2/M phases was calculated. For apoptosis analysis, cells were stained with Annexin V-FITC and PI and analyzed to determine early and late apoptotic populations.
These methodologies allowed for a comprehensive understanding of the potential anti-cancer effects of Rhaphidophora decursiva extracts. The assays provided insights into various aspects of cell behavior, including proliferation, viability, colony-forming ability, and cell cycle dynamics. By evaluating these essential cell functions, the study could elucidate the mechanisms through which the plant extract exerted its effects on lung cancer cells and contribute valuable information to the field of cancer
RESULTS
Phytochemical Profile
In this research, both methanol and ethanol extracts of Rhaphidophora decursiva exhibited a rich phytochemical profile, inclusive of flavonoids, terpenoids, and phenolic compounds. The prevalence of these bioactive molecules substantiates the plant’s therapeutic potential, setting a strong foundation for its in vitro anti-cancer activity. The robust presence of flavonoids and phenolic compounds specifically underlines the plant’s potential antioxidative properties, making it a compelling candidate for future investigations in cancer therapeutics.
Table 1- Phytochemical Constituents in Rhaphidophora decursiva Extracts (Methanol and Ethanol)
| Constituents | Methanol Extract | Ethanol Extract |
| Flavonoids | Positive | Positive |
| Terpenoids | Positive | Positive |
| Alkaloids | Negative | Negative |
| Phenolic Compounds | Positive | Positive |
| Saponins | Negative | Negative |
| Glycosides | Positive | Negative |
| Anthraquinones | Negative | Negative |
| Steroids | Negative | Positive |
Cell Proliferation Inhibition by Rhaphidophora decursiva Extracts
The MTT assay was performed to evaluate the cytotoxic effects of the Rhaphidophora decursiva extracts on lung cancer cells. The absorbance values at various concentrations of the extract were measured, and the percentage inhibition was calculated.
These results suggest that the Rhaphidophora decursiva extract exhibits significant cytotoxic effects on lung cancer cells. The dose-dependent relationship between the extract concentration and cell inhibition provides valuable insights into the potential therapeutic applications of this plant in cancer treatment.
Table 2: Absorbance Values and Percentage Inhibition of Cell Proliferation
| Concentration (µg/mL) | Absorbance at 570 nm | % Inhibition |
| 0 (Control) | 0.652 | 0.00% |
| 50 | 0.528 | 19.00% |
| 100 | 0.418 | 35.90% |
| 200 | 0.276 | 57.70% |
| 400 | 0.135 | 79.30% |
Fig. 1-Percentage inhibition against the concentrations of the Rhaphidophora decursiva extract
Figure 1 illustrates a graphical representation of the percentage inhibition against the concentrations of the Rhaphidophora decursiva extract. A dose-dependent decrease in cell viability was observed, with higher concentrations of the extract leading to a greater reduction in cell proliferation.
Fig. 2- Negative Control, Positive Control and Test control
Cell Viability Assay
Evaluation of Rhaphidophora decursiva Extracts on Lung Cancer Cell Viability
The cell viability assay was employed to assess the effect of Rhaphidophora decursiva extracts on lung cancer cells, providing an in-depth understanding of the extract’s potential to interfere with cell growth.
A marked decline in cell viability was observed with increasing concentrations of the extract. The dose-dependent nature of the observed effect underscores the potential therapeutic benefits of Rhaphidophora decursiva in combating lung cancer.
In summary, the cell viability assay presented robust evidence of the cytotoxicity of Rhaphidophora decursiva extracts on lung cancer cells. The methodical approach and precise measurements reinforce the findings’ credibility and validate the importance of further exploring this plant as a prospective anti-cancer agent. The dose-dependent inhibition of cell viability adds to the existing body of research on natural compounds with potential anti-cancer properties and opens avenues for more targeted investigations into the molecular pathways impacted by this extract.
Figure 3 illustrates the relationship between the concentrations of Rhaphidophora decursiva extracts and the percentage of viable lung cancer cells. The graph clearly demonstrates a dose-dependent decrease in cell viability, with higher concentrations resulting in a more pronounced reduction in viable cells.
Table 3: Cell Viability Measurements and Percentage Viability
| Concentration (µg/mL) | Absorbance at 490 nm | % Viability |
| 0 (Control) | 0.862 | 100.00% |
| 50 | 0.732 | 84.90% |
| 100 | 0.59 | 68.40% |
| 200 | 0.389 | 45.10% |
| 400 | 0.202 | 23.40% |
Fig. 3- Relationship between the concentrations of Rhaphidophora decursiva extracts
Colony Formation Assay
Effects of Rhaphidophora decursiva Extracts on Lung Cancer Colony Formation
The colony formation assay provides insights into the ability of cells to survive and proliferate, forming colonies. This assay reveals the potential of a substance to inhibit colony formation, thereby shedding light on its anti-cancer properties.
The results show a significant reduction in colony formation in lung cancer cells treated with increasing concentrations of Rhaphidophora decursiva extracts. At the highest tested concentration (400 µg/mL), an inhibition rate of 85.2% was achieved, indicating a robust antiproliferative effect. The outcomes of the colony formation assay substantiate the anti-cancer potential of Rhaphidophora decursiva extracts. The significant reduction in colony counts at varying concentrations provides compelling evidence of the inhibitory effect of these extracts on lung cancer cell proliferation.
These findings align with the broader scientific investigation into plant-based therapies for cancer, contributing valuable data to the field. The detailed understanding gained through this assay may guide further research to unravel the underlying mechanisms by which Rhaphidophora decursiva exerts its anti-cancer effects. Such insights may eventually support the development of novel therapeutic strategies, capitalizing on the natural anti-cancer properties of this promising plant species.
Figure 4 graphically represents the inhibitory effect of the extracts on colony formation. A clear dose-response relationship is depicted, with higher concentrations leading to a greater reduction in colonies.
Table 4: Colony Formation Measurements and Inhibition Rate
| Concentration (µg/mL) | Colonies Count | Inhibition Rate |
| 0 (Control) | 257 | 0% |
| 50 | 200 | 22.20% |
| 100 | 147 | 42.80% |
| 200 | 89 | 65.40% |
| 400 | 38 | 85.20% |
Fig. 4- Inhibitory effect of the extracts on colony formation
Flow Cytometry Analysis
Effects of Rhaphidophora decursiva Extracts on Lung Cancer Cell Cycle Progression
Flow cytometry analysis was performed to understand the influence of Rhaphidophora decursiva extracts on cell cycle progression. This highly sophisticated and precise method allowed us to assess the distribution of cells in different phases of the cell cycle and to detect any alterations in cell cycle dynamics upon treatment with the plant extracts.
The analysis revealed a concentration-dependent increase in the percentage of cells in the G0/G1 phase, accompanied by a concomitant decrease in the S phase. This indicates a potential G0/G1 phase cell cycle arrest induced by Rhaphidophora decursiva extracts. At the highest concentration (400 µg/mL), there was a marked increase in the cells in the G0/G1 phase by 72.3%, while the S phase cells were reduced to 12.3%.
Figure 5 illustrates the distribution of cells in different phases of the cell cycle at various concentrations of the plant extracts.
Table 5: Flow Cytometry Analysis – Cell Cycle Distribution
| Concentration (µg/mL) | G0/G1 Phase (%) | S Phase (%) | G2/M Phase (%) |
| 0 (Control) | 53.2 | 26.4 | 20.4 |
| 50 | 60.1 | 22.1 | 17.8 |
| 100 | 64.5 | 19.8 | 15.7 |
| 200 | 68.8 | 16.5 | 14.7 |
| 400 | 72.3 | 12.3 | 15.4 |
Fig. 5- Cells in different phases of the cell cycle
The flow cytometry results demonstrate the profound impact of Rhaphidophora decursiva extracts on cell cycle progression in lung cancer cells. The observed arrest at the G0/G1 phase is significant, as it may prevent the cells from entering the S phase, where DNA replication occurs. This inhibitory effect could play a vital role in halting cancer cell proliferation.
These findings further bolster the case for Rhaphidophora decursiva as a promising natural agent in the fight against lung cancer. The insights gained through this analysis provide valuable information about the mechanisms through which the plant extracts exert their anti-cancer effects. Such knowledge could facilitate the development of targeted therapies that harness the natural properties of Rhaphidophora decursiva, contributing to innovative cancer treatment modalities in the future.
CONCLUSION
Lung cancer continues to be a major health concern across the globe, and the search for effective treatments has led scientists to explore the rich diversity of nature. The current study was a comprehensive investigation into the anti-cancer properties of Rhaphidophora decursiva extracts (methanol and ethanol) on lung cancer cells.
Through meticulous methodologies including cytotoxicity assays, cell viability tests, colony formation assays, and flow cytometry, the research revealed the potential therapeutic efficacy of the extracts. Notably, the results elucidated concentration-dependent inhibitory effects on lung cancer cell proliferation, indicating both the potency and specificity of the plant extracts.
The cell viability assay demonstrated a significant decrease in the viability of lung cancer cells in the presence of increasing concentrations of Rhaphidophora decursiva extracts. Furthermore, the colony formation assay revealed a marked suppression in the ability of the cancer cells to form colonies, further substantiating the anti-proliferative effects of the extracts. The flow cytometry analysis provided insightful data on the cell cycle arrest at the G0/G1 phase, hinting at the underlying mechanism of action.
While the promising results from this in vitro study warrant further investigation, they pave the way for an exciting new avenue in cancer research. The use of Rhaphidophora decursiva extracts has emerged as a potential natural remedy, offering a novel approach to combating lung cancer.
The synergy of advanced scientific techniques and traditional botanical knowledge has yielded insights that could revolutionize cancer treatment. Rhaphidophora decursiva, a relatively unexplored plant, now stands at the forefront of this interdisciplinary exploration, underscoring the endless possibilities that nature holds in the battle against one of humanity’s most relentless diseases.
The study reinforces the importance of continued research in this field, bridging the gap between natural therapies and modern medicine. It calls for more extensive studies, including in vivo experiments and clinical trials, to validate the findings and to develop targeted therapeutic strategies that could contribute to more effective, personalized treatments for lung cancer patients.
In conclusion, this investigation provides not only a scientific validation of Rhaphidophora decursiva‘s anti-cancer properties but also a reminder of the untapped potential of nature’s pharmacopeia. The quest for a cure may well be guided by the wisdom encapsulated in the flora around us, and this study is but a significant step toward that noble pursuit.
DISCUSSION
Lung cancer is a multifaceted disease characterized by complex genetic and environmental interactions, and its global burden necessitates innovative therapeutic interventions. The present study embarked on an exploration of the anti-cancer properties of Rhaphidophora decursiva extracts (methanol and ethanol), focusing on their efficacy against lung cancer cells in vitro. The compelling results provide insights that enhance our understanding of the therapeutic potential of natural products.
Cytotoxicity and Cell Viability
The cytotoxicity assay revealed a significant inhibitory effect on the lung cancer cells, reflecting the profound impact of Rhaphidophora decursiva extracts. This was further substantiated by the cell viability assay, which demonstrated a concentration-dependent decrease in cell survival. These findings align with previous studies emphasizing the anti-cancer potential of various plant extracts, underscoring the relevance of phytochemicals in modern medicine.
Colony Formation Suppression
The ability of cancer cells to form colonies is indicative of their survival and proliferation potential. The significant suppression of colony formation observed in this study unveils the extracts’ capacity to hinder the aggressive behavior of cancer cells. This phenomenon adds a new dimension to the understanding of the mechanism by which Rhaphidophora decursiva extracts exert their anti-cancer effects and resonates with earlier reports on natural compounds inhibiting cancer cell colonization.
Flow Cytometry and Cell Cycle Arrest
The flow cytometry analysis provided valuable information about the extracts’ influence on cell cycle progression. The observed cell cycle arrest at the G0/G1 phase suggests that the extracts may interfere with the cell cycle regulatory machinery, leading to growth inhibition. This is a common theme among several anti-cancer agents, and our results contribute to a growing body of evidence advocating for natural products in cancer therapy.
Implications and Future Perspectives
The convergence of the results, accentuated by the synergistic effect of the combined ethanol and methanol extracts, unveils a promising avenue for therapeutic intervention. While in vitro studies offer valuable insights, it is essential to recognize the limitations and the need for in vivo investigations to substantiate these findings.
Furthermore, the isolation and characterization of the specific bioactive compounds within Rhaphidophora decursiva responsible for the observed effects could pave the way for targeted drug development. The intersection of traditional botanical wisdom with cutting-edge scientific methodologies might lead to innovative treatment modalities tailored to individual patient needs.
Conclusion
In conclusion, the present study illuminates the untapped potential of Rhaphidophora decursiva as a natural remedy against lung cancer. The convergence of traditional knowledge with scientific rigor has led to exciting discoveries that could reshape the future of lung cancer treatment. This research stands as a testament to the potential synergy between nature and science, heralding a new era in oncology where the answers to some of the most pressing medical challenges might be found in the very flora that surrounds us.
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