A Review on “A study of Anti Cancer Herb Vinca Rosea”

A Review on “A study of Anti Cancer Herb Vinca Rosea”

Aman Khan*, Prof. Rajkumari Lodhi, Dr. Satish Nayak

Department of Pharmacy, Bansal Collge of Pharmacy, India

DOI: https://doi.org/10.51244/IJRSI.2025.12040154

Received: 12 May 2025; Accepted: 14 May 2025; Published: 24 May 2025

ABSTRACT

Vinca rosea, also called Catharanthus roseus or Madagascar periwinkle, is a widely recognized medicinal plant extensively researched for its strong anti-cancer properties. This review provides an in-depth look at the plant’s phytochemical composition, pharmacological effects, and therapeutic potential, with a particular focus on its role in cancer treatment. Vinca rosea is a valuable source of bioactive alkaloids, such as vincristine and vinblastine, which have been developed into effective chemotherapy drugs used to treat a variety of cancers, including leukemia, lymphoma, breast cancer, and lung cancer. These compounds primarily work by disrupting microtubule dynamics, which inhibits cell division and induces apoptosis in cancer cells. In addition to its clinical relevance, the review also examines the biological mechanisms behind its anti-cancer effects, current drug formulations and their pharmaceutical applications, toxicity levels, and challenges in drug development. Moreover, it discusses efforts to conserve the plant and biotechnological methods aimed at improving the sustainable production of these valuable alkaloids. By summarizing existing knowledge and highlighting research gaps, the paper emphasizes the importance of Vinca rosea in natural product-based cancer therapies and advocates for further exploration of its clinical potential and bioengineering applications.

Keywords: Vinca rosea, Catharanthus roseus, Bioengineering, leukemia, lymphoma, Madagascar periwinkle.

INTRODUCTION

Vinca rosea, commonly known as Madagascar periwinkle, is a herbaceous plant native to Madagascar but now widely found in tropical and subtropical regions across the globe. The plant has gained significant attention due to its rich variety of bioactive compounds, especially alkaloids, which have shown considerable pharmacological activity. Among its many traditional medicinal applications, one of the most notable is its use in cancer treatment. The alkaloids of Vinca rosea, particularly vincristine and vinblastine, have been isolated and developed into widely used chemotherapy drugs that have transformed cancer treatment, particularly in the management of leukemia, Hodgkin’s lymphoma, and other cancers.

As interest in herbal remedies and plant-based therapies has surged in modern medicine, Vinca rosea has been extensively studied for its anti-cancer properties. This review aims to provide a thorough exploration of its pharmacological potential, with a focus on its effectiveness against cancer. It examines the plant’s traditional uses, its chemical components, the mechanisms through which its alkaloids combat cancer, and the clinical challenges and applications related to their use.

Cancer continues to be a leading global cause of death, and the demand for more effective, less toxic therapies is greater than ever. Although conventional chemotherapy has made significant strides in cancer treatment, it often comes with severe side effects. Therefore, developing more targeted and less toxic therapies, such as those derived from natural sources like Vinca rosea, offers considerable promise. This review outlines the current understanding of how Vinca rosea contributes to cancer treatment and highlights its future potential in clinical and biotechnological applications.

Taxonomy and Botanical Profile

Vinca rosea belongs to the Apocynaceae family, which includes a variety of tropical and subtropical plants. It is also referred to by several other names, including Catharanthus roseus, Madagascar periwinkle, and old-maid plant. While native to Madagascar, it is now widely cultivated in tropical and subtropical regions, including Asia, Africa, and the Mediterranean.

Scientific Classification

• Kingdom: Plantae
• Division: Angiosperms
• Class: Eudicots
• Order: Gentianales
• Family: Apocynaceae
• Genus: Vinca
• Species: Vinca rosea

MORPHOLOGY

Vinca rosea is a perennial herb that can grow to about 1–2 feet (30–60 cm) in height. It has a woody base, with smooth, glossy green leaves that are arranged oppositely. The plant produces bright, funnel-shaped flowers, usually pink or white, with five petals, blooming year-round in tropical climates. These flowers are often used in ornamental gardening for their vibrant colors and ease of cultivation.

• Leaves: The leaves are oval to lance-shaped, 4–9 cm long, deep green, smooth, and leathery. They grow in pairs opposite each other along the stems.
• Flowers: The flowers are typically pink or white and feature a distinctive five-petaled, funnel-shaped structure. They are fragrant and attract pollinators like bees and butterflies.
• Roots: The root system is fibrous, which makes it easy to propagate. The plant is somewhat drought-tolerant due to its shallow root system, though it still requires well-draining soil for optimal growth.

Habitat and Geographical Distribution

Native to Madagascar, Vinca rosea thrives in tropical and subtropical climates. Over time, it has spread to other parts of the world, including Asia, India, and the Mediterranean. The plant prefers well-drained, slightly acidic soils and can often be found in gardens, fields, and roadsides. It adapts well to warm climates and grows in various soil types, making it an ideal candidate for cultivation in diverse regions.

As it is widely used in both ornamental gardening and the pharmaceutical industry, Vinca rosea is cultivated in many countries. Large-scale cultivation is especially crucial for the production of alkaloid compounds such as vincristine and vinblastine, which are harvested for cancer treatments.

Propagation and Cultivation

Vinca rosea can be propagated by seeds, cuttings, or tissue culture. In agricultural settings, cuttings or micropropagation are typically used to ensure uniformity in alkaloid production. The plant thrives in full sunlight but can tolerate partial shade. It prefers moderately rich, well-draining soils and requires regular watering, especially in dry periods. However, overwatering should be avoided to prevent root rot.

Economic Importance

In addition to its traditional medicinal applications, Vinca rosea holds substantial economic value due to the extraction of its alkaloids for the pharmaceutical industry. It has become a vital crop in tropical regions, grown both for ornamental purposes and for its medicinal properties. The plant’s role in producing anti-cancer drugs like vincristine and vinblastine has elevated its importance in pharmaceutical research and development.

Phytochemistry of Vinca rosea

Vinca rosea, a rich source of bioactive compounds, has gained significant attention, particularly for its cancer-fighting properties. The plant contains a diverse range of chemical constituents, with alkaloids being the most studied and important class. Among these, vincristine and vinblastine stand out as the most therapeutically valuable alkaloids, extensively researched for their anti-cancer effects.

Major Bioactive Compounds

Alkaloids

Alkaloids are the primary active compounds in Vinca rosea and play a key role in the plant’s medicinal properties, especially in treating cancer. The major alkaloids include:

• Vincristine: Vincristine is one of the most potent alkaloids from Vinca rosea, widely used in treating cancers like leukemia, Hodgkin’s lymphoma, and certain breast cancers. It works by inhibiting microtubule formation, disrupting cell division, and inducing apoptosis (programmed cell death) in cancer cells.
• Vinblastine: Similar to vincristine, vinblastine is used in chemotherapy treatments for cancers such as Hodgkin’s lymphoma, testicular cancer, and Kaposi’s sarcoma. It also prevents tubulin polymerization, thus inhibiting microtubule formation and halting cell division.

Other minor alkaloids with potential therapeutic value in Vinca rosea include:

• Vindoline: A precursor to vincristine and vinblastine, with some anti-cancer properties, though less potent.
• Catharanthine: Another indole alkaloid involved in the synthesis of vincristine and vinblastine, studied for its bioactivity but less significant in cancer treatment.

Flavonoids

Flavonoids in Vinca rosea exhibit antioxidant, anti-inflammatory, and anti-cancer properties. Common flavonoids in the plant include:

• Quercetin
• Kaempferol

These compounds can enhance the effects of alkaloids by inducing apoptosis, inhibiting tumor growth, and preventing metastasis. They also regulate signalling pathways that control cell survival and proliferation.

Tannins

Tannins are polyphenolic compounds in Vinca rosea with antioxidant properties. They are linked to reducing oxidative stress, which is a major factor in cancer development. While their direct role in cancer treatment is still under investigation, their antioxidant and anti-inflammatory effects make them important in cancer prevention.

Other Compounds

• Steroids and Saponins: These compounds contribute to the plant’s medicinal effects, with some exhibiting immune-modulatory properties that may complement the anti-cancer actions of alkaloids.
• Glycosides: Various glycosides in Vinca rosea have been explored for their potential cytotoxic effects on cancer cells, though they are generally less potent than the alkaloids.

Extraction and Isolation of Compounds

Alkaloids, particularly vincristine and vinblastine, are primarily isolated from the leaves and stems of Vinca rosea. The extraction process includes:

• Solvent Extraction: Organic solvents like ethanol or methanol are used to extract alkaloids from dried plant material.
• Column Chromatography: This technique helps purify the alkaloids, separating them from other plant compounds.
• High-Performance Liquid Chromatography (HPLC): HPLC is used for final purification and quantification, ensuring that alkaloids meet pharmaceutical standards.

Recent biotechnological advances, such as plant tissue culture and genetic engineering, have improved the efficiency of vincristine, vinblastine, and related compound production, helping meet global demand for cancer therapies. The authors may consider including a table that summarizes the phytochemicals extracted from various parts of Vinca rosea, along with relevant citations and studies on their effects across different types of cancer.

Role of Biotechnology in Enhancing Alkaloid Production

To increase the yield of vincristine and vinblastine, biotechnological techniques have been explored. Methods such as genetic modification, cell suspension cultures, and synthetic biology have been used to enhance alkaloid production in laboratory conditions. Additionally, bioreactors and genetically engineered microbial systems are being studied as alternative large-scale production methods to tackle overharvesting and conserve Vinca rosea.

Mechanism of Anti-Cancer Action

The anti-cancer properties of Vinca rosea are primarily attributed to its alkaloids vincristine and vinblastine, which disrupt essential cellular processes required for cell division. The key mechanisms include the inhibition of microtubule polymerization, cell cycle arrest, and induction of apoptosis in cancer cells.

Inhibition of Microtubule Formation

Both vincristine and vinblastine bind to tubulin, a protein that forms microtubules, crucial components of the cytoskeleton. Microtubules are essential during mitosis, as they help form the mitotic spindle needed for chromosome separation.

• These alkaloids prevent tubulin from polymerizing into microtubules, disrupting spindle formation and halting mitosis.
• As a result, cells are arrested in metaphase, where chromosomes align at the cell’s equator but cannot separate properly.
• This arrest leads to mitotic catastrophe, a type of cell death caused by failed mitosis.

Cell Cycle Arrest

By inhibiting microtubule formation, vincristine and vinblastine also interfere with the normal progression of the cell cycle, specifically at the G2/M phase, where cells prepare for mitosis.

• Arrest at this stage prevents cancer cells from proliferating and accumulating further genetic damage.
• Cells are either unable to progress through the cycle, leading to cell death or senescence (a state where cells stop dividing but remain metabolically active).

Induction of Apoptosis

Vincristine and vinblastine also trigger apoptosis, a controlled form of cell death that eliminates damaged or cancerous cells.

• These alkaloids activate pro-apoptotic signaling pathways and inhibit anti-apoptotic proteins.
• They increase the expression of p53, a tumor suppressor that plays a key role in initiating apoptosis in response to DNA damage.
• Additionally, they activate caspases, enzymes that execute apoptosis by breaking down cellular components, leading to the death of cancer cells.

Anti-Angiogenesis Effects

Vincristine and vinblastine may also contribute to anti-angiogenesis, the prevention of new blood vessel formation. Tumors rely on angiogenesis to supply oxygen and nutrients for growth.

• By disrupting microtubules, these alkaloids hinder the formation of blood vessels, depriving the tumor of necessary resources
• This anti-angiogenic activity helps shrink tumors and reduces metastasis

Effect on Cancer Stem Cells

Emerging studies suggest that vincristine and vinblastine can target cancer stem cells (CSCs), a subpopulation of cells that are often resistant to conventional therapies and contribute to tumor recurrence.

• Vincristine has shown the potential to inhibit the self-renewal properties of CSCs, reducing their ability to regenerate new tumors.
• Targeting CSCs enhances the therapeutic value of these alkaloids, particularly in combination therapies aimed at preventing cancer relapse.

Synergistic Effects with Other Chemotherapeutic Agents

Vincristine and vinblastine are often used in combination with other chemotherapy drugs, such as methotrexate, cyclophosphamide, and doxorubicin, to improve treatment effectiveness. This synergistic approach enhances the overall anti-cancer activity by targeting different mechanisms of cancer cell survival.

• Synergyoccurs when drugs work together in a way that their combined effect is greater than the sum of their individual effects.
• Vincristine and vinblastine arrest the cell cycle and induce apoptosis, complementing the DNA-damagingeffects of other chemotherapy agents. This synergy leads to more effective tumor destruction.

By combining drugs with different mechanisms of action, chemotherapy regimens become more potent, reducing the chance of cancer cells surviving and evolving resistance to treatment.

Resistance Mechanisms and Challenges

Despite their effectiveness, vincristineandvinblastine face challenges due to the development of drug resistance by cancer cells. The resistance mechanisms include:

• Overexpression of P-glycoprotein (P-gp): This membrane protein pumps out vincristine and vinblastine from cancer cells before they can exert their therapeutic effects, reducing drug efficacy.
• Mutations in Tubulin: Changes in tubulin can prevent vincristine and vinblastine  from binding effectively, which is crucial for their action in inhibiting microtubule formation.

To overcome these resistance mechanisms, researchers are focusing on developing combination therapies and creating new drug analogs that can bypass or counteract these resistance pathways.

Pharmacological and Clinical Studies

The pharmacological properties of Vinca rosea, particularly its anti-cancer effects, have been extensively studied in vitro (laboratory) and in vivo (animal) models, as well as human clinical trials. The bioactive compounds vincristine and vinblastine have been developed into widely used chemotherapy drugs. This section explores various studies assessing the pharmacological efficacy and clinical applications of Vinca rosea and its alkaloids.

In Vitro Studies

In vitro studies using cancer cell lines have shown that vincristine and vinblastine possess potent anti-cancer properties.

• Cancer Cell Line Studies: Researchers have treated various cancer cell lines, including those for leukemia, breast cancer, lung cancer, and ovarian cancer, with these alkaloids to assess their effects on cell viability, proliferation, apoptosis, and cell cycle progression.
• Vincristine has demonstrated significant cytotoxicity against acute lymphoblastic leukemia (ALL) cells, leading to high rates of apoptosis.
• Vinblastine has shown substantial anti-proliferative effects on breast cancer cells, even those resistant to other chemotherapeutic agents.
• Mechanistic Insights: In vitro studies have confirmed that both vincristine and vinblastine inhibit microtubule formation, disrupt mitosis, and induce mitotic arrest in cancer cells. Additionally, they activate caspases, key apoptotic enzymes, further triggering cell death.
• Synergistic Effects: Studies have also examined the combined effects of vincristine and vinblastine with other anti-cancer agents, such as doxorubicin, paclitaxel, and cisplatin. These combinations have shown enhanced efficacy in killing cancer cells, with greater reductions in cell viability compared to monotherapies.

In Vivo Studies

Animal studies further support the anti-cancer efficacy of vincristine and vinblastine in vivo, where the compounds are administered to animals with implanted tumors.

• Tumor Growth Inhibition: In various animal models of cancer, both alkaloids have significantly inhibited tumor growth.
• In a human breast cancer xenograft model, vincristine reduced tumor size and slowed metastatic growth.
• Vinblastine has been shown to effectively reduce tumor volume in testicular cancer and Hodgkin’s lymphoma
• Combination with Other Agents: In vivo studies support combining vincristine with cyclophosphamide, showing that the combination results in more significant tumor regression than using either drug alone.
• Pharmacokinetics and Biodistribution: Studies on the pharmacokinetics of vincristine and vinblastine have provided valuable information on their absorption, distribution, metabolism, and elimination. For example, vincristine can cross the blood-brain barrier, leading to widespread tissue distribution, which is important for treating certain types of cancer.

Clinical Studies in Humans

Clinical studies have established the clinical value of vincristine and vinblastine in treating various cancers, solidifying their role in multi-drug chemotherapy regimens.

• Vincristine in Leukemia: Vincristine is a cornerstone treatment for acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma. Clinical trials, including a study published in The Lancet, have demonstrated that vincristine, as part of combination chemotherapy, significantly improves remission rates in pediatricleukemia patients.
• Vinblastine in Lymphomas and Testicular Cancer: Vinblastine plays a key role in treating Hodgkin’s lymphoma and testicular cancer. When combined with other drugs, such as bleomycin and dacarbazine, vinblastine has improved survival rates in lymphoma patients. In testicular cancer, it effectively reduces tumor size and prevents metastasis.
• Toxicity and Side Effects: Despite their effectiveness, both drugs are associated with side effects, primarily neurotoxicity, leading to peripheral neuropathy. Other side effects include nausea, vomiting, bone marrow suppression, and hair loss. Additionally, these drugs can cause immunosuppression, increasing the risk of infections during chemotherapy.
• Management of Toxicity: To manage these toxicities, strategies such as dose adjustments, the use of neuroprotective agents, and the development of liposomal formulations are being explored to target the drug more specifically to tumor tissues, reducing systemic toxicity.

Future Directions in Clinical Use

Research continues to explore ways to improve the therapeutic index of vincristine and vinblastine by reducing side effects and overcoming resistance. Promising directions include:

• Nanoparticle-based Drug Delivery: Developing nanocarrier systems that can encapsulate vincristine and vinblastine to target tumors more precisely while minimizing off-target effects and systemic toxicity.
• Combination Therapies: Combining these alkaloids with newer targeted therapies, immune checkpoint inhibitors, or monoclonal antibodies is an area of active investigation. Such combinations may enhance the anti-cancer effects and improve outcomes for patients with resistant tumours.
• Personalized Medicine: Advances in genetic profiling of tumors allow for personalized treatment plans. Identifying specific molecular markers will help determine which patients will benefit most from vincristine and vinblastine-based therapies, optimizing treatment regimens.

Formulations and Drug Development

The alkaloids vincristine and vinblastine, derived from Vinca rosea, have been vital in the development of chemotherapy treatments for various cancers. However, their clinical use comes with significant side effects such as neurotoxicity and myelosuppression. As a result, ongoing research is focused on improving these drugs’ delivery mechanisms and developing novel formulations to enhance their therapeutic potential while minimizing adverse effects. This section reviews the formulations and strategies aimed at improving vincristine and vinblastine’s efficacy and safety profiles.

Conventional Drug Formulations

Traditionally, vincristine and vinblastine have been administered via intravenous (IV) infusion in standard chemotherapy protocols. These formulations are typically available as lyophilized powders that must be reconstituted before injection.

• Administration: Vincristine sulphate and vinblastine sulphate are commonly delivered through IV infusion, aiming for effective drug distribution to cancerous tissues. The frequency of administration varies based on cancer type and treatment regimen, typically occurring weekly or every 2-3 weeks.
• Limitations:
• Systemic Toxicity: Both drugs are associated with neurotoxicity, potentially resulting in peripheral neuropathy and other neurological issues.
• Limited Bioavailability: Due to poor solubility and a short haonal formulations may not achieve optimal drug concentrations at the tumour site.
• Non-targeted Delivery: Healthy tissues can also be exposed to toxic effects, leading to side effects such as nausea, vomiting, hair loss, and bone marrow suppression.

Liposomal Formulations

Liposomal formulations offer a promising solution to improve the pharmacokinetics and therapeutic index of vincristine and vinblastine. Liposomes, spherical vesicles made of lipid bilayers, encapsulate the drugs within their core, enhancing controlled and targeted delivery.

• Enhanced Stability and Solubility: Liposomal formulations improve the drugs’ stability and solubility, prolonging their circulation time and reducing exposure to healthy tissues.
• Tumour Targeting: The enhanced permeability and retention (EPR) effect allows liposomes to accumulate preferentially in tumor tissues, improving localized drug concentrations while minimizing systemic toxicity.
• Clinical Outcomes: Liposomal vincristine has demonstrated reduced neurotoxicity and improved pharmacokinetic profiles in clinical trials, indicating its potential as a more selective cancer treatment.

Nanoparticle-Based Drug Delivery Systems

In addition to liposomal formulations, nanoparticle-based drug delivery systems (DDS) provide a cutting-edge approach for enhancing vincristine and vinblastine specificity and efficacy.

• Polymeric Nanoparticles: These can encapsulate vincristine and vinblastine, offering controlled, sustained release. Functionalizing nanoparticles with targeting ligands such as antibodies or peptides can enhance the drugs’ specificity for cancer cells.
• Gold and Silica Nanoparticles: These nanoparticles possess intrinsic properties, such as photo thermal therapy capabilities or immune modulation, which can enhance anti-cancer effects while serving as drug carriers.
• Magnetic Nanoparticles: Magnetic nanoparticles can be directed to tumor sites using external magnetic fields, further increasing the precision of drug delivery.

Advantages

• Targeted Drug Delivery: Nanoparticles ensure that drugs are delivered to the tumor site with minimal off-target effects.
• Reduced Toxicity: By lowering drug concentrations in healthy tissues, nanoparticle-based systems can reduce systemic side effects like neurotoxicity and bone marrow suppression.
• Improved Stability: These systems enhance the solubility and stability of vincristine and vinblastine, facilitating more efficient treatment with lower drug doses.

Targeted Delivery with Antibody-Drug Conjugates (ADCs)

Antibody-drug conjugates (ADCs) are another promising approach to enhance the efficacy of vincristine and vinblastine. ADCs consist of a monoclonal antibody linked to a cytotoxic drug, allowing for targeted delivery to tumor cells.

• Targeting Tumor-Specific Antigens: ADCs can target antigens like HER2/neu, EGFR, or CD20, which are overexpressed in various cancers such as breast cancer and non-Hodgkin lymphoma. By linking vincristine or vinblastine to these antibodies, the chemotherapy drugs can be delivered directly to cancer cells.
• Preclinical Success: Vincristine-conjugated ADCs have shown enhanced anti-cancer effects in preclinical studies. Clinical trials are ongoing to evaluate the safety and efficacy of these targeted treatments.

Biotechnological Approaches and Synthetic Biology

Advances in synthetic biology and genetic engineering have opened new possibilities for producing vincristine and vinblastine. Traditionally derived from Vinca rosea, large-scale production is limited due to low yields and complex extraction processes.

• Synthetic Biology: Researchers are working on engineering microorganisms or cell cultures to produce these alkaloids, potentially providing a more sustainable and scalable production method.
• Plant Tissue Culture: Bioreactor systems and plant tissue culture techniques are being explored to enhance production, reducing the need for wild plant harvests, which can be unsustainable.

Challenges and Future Directions

While significant progress has been made in developing improved formulations and drug delivery systems, several challenges remain:

• Drug Resistance: Cancer cells can develop resistance to vincristine and vinblastine, often through over expression of P-glycoprotein (P-gp) and other efflux pumps. Developing formulations that bypass these resistance mechanisms remains an active area of research.
• Target Specificity: Although targeted delivery systems hold promise, further research is necessary to optimize tumour-specific targeting without affecting normal cells.
• Toxicity: Neurotoxicity continues to be a major concern despite the development of liposomal and nanoparticle-based systems. Ongoing efforts to reduce these side effects will be critical for improving patient outcomes.

Future Research Directions:

• Combination Therapies: Combining vincristine and vinblastine with newer therapies, such as targeted therapies or immunotherapies, could overcome resistance and improve treatment outcomes.
• Personalized Medicine: Genetic profiling and precision medicine are becoming essential in tailoring vincristine and vinblastine therapies, optimizing efficacy while minimizing side effects.

CONCLUSION

Vinca rosea has had a profound impact on cancer treatment, with its alkaloids vincristine and vinblastine forming cornerstone treatments in chemotherapy regimens. Their mechanisms of action—disrupting microtubule formation, inducing mitotic arrest, and promoting apoptosis—have made them highly effective in treating cancers such as leukemia, lymphomas, breast cancer, and testicular cancer.

Despite their effectiveness, vincristine and vinblastine are associated with toxicity, particularly neurotoxicity. This has driven the development of advanced drug delivery systems, including liposomal formulations, nanoparticle-based delivery systems, and antibody-drug conjugates, all designed to enhance targeted delivery and reduce systemic toxicity. These innovations have shown promise in improving therapeutic efficacy and minimizing side effects, while ongoing research into biotechnological approaches and synthetic biology offers a sustainable path forward for large-scale production.

In conclusion, while significant challenges such as drug resistance and toxicity remain, the continued exploration of Vinca rosea and its alkaloids, particularly through advanced formulations and combination therapies, holds great promise for the future of cancer treatment. As personalized medicine continues to evolve, these compounds may play an even greater role in optimizing cancer care and improving outcomes for patients worldwide.

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