CURCUMIN: A COMPREHENSIVE REVIEW OF IT'S POTENTIAL AGAINST CANCER AND ASSOCIATED COMPLICATIONS

International Journal of Pharmaceutical Science and Health Care Volume 15, Number 6, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17602078 Original Article ©2025 RS Publication, rsp[email protected]m 58 CURCUMIN: A COMPREHENSIVE REVIEW OF IT’S POTENTIAL AGAINST CANCER AND ASSOCIATED COMPLICATIONS Souvik Bose 1 , Soumen Dey* 1, Sayan Roy 2 , Animish Sahu 2 , Tekchand Senapati 3 1 Department of Pharmacy, Sanaka Educational Trust’s Group of Institutions, Maulana Abul Kalam Azad University of Technology, West Bengal, India 2 Department of Pharmacy, One Beat College of Medical Sciences, Uttar Pradesh, India 3 Department of Pharmacy, The Pharmaceutical College, Barpali, Odisha, India ARTICLE INFO ABSTRACT ©2025 RS Publication Paper ID: IJPHC6914CE9F1DD86 Received: 2025-10-08 Published: 2025-11-13 DOI: https://dx.doi.org /10.5281/zenodo.17 602078 Page No: 58-70 Curcumin, a bioactive polyphenolic chemical obtained from the rhizome of Curcuma longa, or turmeric, has drawn a lot of interest due to its strong pharmacological characteristics, especially its potential to treat cancer. Curcumin's capacity to alter several cellular signalling pathways implicated in the development, spread, and metastasis of cancer has been extensively studied. It has anti-proliferative, proapoptotic, anti-inflammatory, and antioxidant effects on lung, prostate, breast, and colorectal malignancies, among other cancer types. Curcumin downregulates oncogenes, increases the expression of tumour suppressor genes, and interferes with transcription factors including NF-κB and STAT3. Curcumin can also make tumour cells more susceptible to traditional chemotherapy and radiation, increasing treatment effectiveness and lowering side effects. Curcumin's quick metabolism, low systemic absorption, and poor bioavailability hinder its clinical translation despite its promising pharmacodynamics. Recent developments include liposomal encapsulation, curcumin analogues that improve stability and bioefficacy, and nanoparticle formulations to address these issues. Curcumin reduces cancer-related side effects such oxidative stress, inflammation, and metabolic dysregulation in addition to its direct anticancer actions. It is a promising addition in integrative cancer therapy due to its broad-spectrum biological actions and safety profile. To fully realise curcumin's therapeutic promise against cancer and its consequences, more research into optimised formulations, dosage standardisation, and carefully planned clinical studies are necessary. Keywords Curcumin, Cancer, Anticancer mechanisms, Inflammation, Nanoparticles, Bioavailability. Corresponding authors name : Soumen Dey, E-mail: soum[email protected] International Journal of Pharmaceutical Science and Health Care Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 Cite This Paper: Souvik Bose, Soumen Dey*, Sayan Roy, Animish Sahu and Tekchand Senapati (2025). "CURCUMIN: A COMPREHENSIVE REVIEW OF IT’S POTENTIAL AGAINST CANCER AND ASSOCIATED COMPLICATIONS". INTERNATIONAL JOURNAL PHARMACEUTICAL SCIENCE AND HEALTH CARE (IJPHC), vol. 15, no. 6, 2025, pp. 58-70. DOI: https://dx.doi.org/10.5281/zenodo.17602078 International Journal of Pharmaceutical Science and Health Care Volume 15, Number 6, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17602078 Original Article ©2025 RS Publication, rsp[email protected]m 59 1.Introduction The brilliant yellow bioactive substance curcumin, which is derived from the rhizome of Curcuma longa, or turmeric, has been thoroughly investigated for a variety of pharmacological and medicinal qualities [1,2]. Curcumin has been utilised for millennia in Chinese and Ayurvedic medicine due to its strong anti-inflammatory, antioxidant, antibacterial, and anticancer properties [3]. Curcumin is a diferuloylmethane polyphenol with a distinct chemical structure that allows it to interact with a variety of molecular targets and signalling pathways in biological systems [4]. Curcumin's potential to prevent and treat a number of chronic diseases, including cancer, has sparked a rise of scientific interest in the past several decades[5]. Cancer, which is characterised by unchecked cell proliferation, apoptosis evasion, angiogenesis, and metastasis, continues to be one of the main causes of illness and death globally[6]. Even though traditional cancer treatments like chemotherapy, radiation, and immunotherapy have evolved significantly, they are still frequently linked to serious side effects, drug resistance, and poor efficacy in advanced stages. Therefore, there is a pressing demand for therapeutic agents that are safer, more effective, and sourced from natural sources. Because of its favourable safety profile and multitargeted method of action, curcumin has become a prospective option [7]. Curcumin interferes with a number of important molecular processes involved in carcinogenesis, according to preclinical research[8]. It inhibits the activation of transcription factors that are important regulators of inflammation, cell survival, and tumour growth, such as nuclear factorkappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3). Curcumin also inhibits angiogenesis, stops metastasis, promotes apoptosis in cancerous cells, and modifies the expression of oncogenes and tumour suppressor genes. Curcumin is a potential chemopreventive and therapeutic agent against a wide range of malignancies, including breast, lung, colorectal, pancreatic, and prostate cancers, due to its diverse effects[9]. In addition to its direct anticancer actions, curcumin is essential for reducing cancer-related side effects like oxidative stress, chronic inflammation, and metabolic disorders [10]. Curcumin helps restore redox balance and shield healthy tissues from oxidative damage by scavenging reactive oxygen species (ROS) and boosting antioxidant enzyme activity. Additionally, its antiinflammatory properties help lessen the tumor-promoting milieu that is frequently created by inflammatory mediators and cytokines [11]. However, curcumin's low systemic absorption, quick metabolism, and poor bioavailability limit its therapeutic use despite these encouraging preclinical results [12]. In order to improve curcumin's solubility, stability, and therapeutic efficacy, current research has concentrated on creating innovative formulations, such as liposomes, phospholipid complexes, nanoparticles, and curcumin analogues. Curcumin's pharmacokinetic profile and target tissue penetration have improved thanks to these novel strategies [13]. International Journal of Pharmaceutical Science and Health Care Volume 15, Number 6, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17602078 Original Article ©2025 RS Publication, rsp[email protected]m 60 All things considered, curcumin is a potent natural substance with great promise for both cancer treatment and prevention. It is a desirable supplement to traditional therapies because to its multitargeted actions and low toxicity. To completely establish curcumin's position as a useful therapeutic agent against cancer and its accompanying consequences, more research into optimised delivery systems, clinical validation, and molecular insights is necessary [14]. 2.Curcumin: Physical Property, Chemistry, and Biosynthesis a. Physical Properties The rhizome of Curcuma longa, or turmeric, yields the hydrophobic polyphenolic chemical curcumin [15]. It is a brilliant yellow crystalline powder that dissolves in organic solvents like ethanol, acetone, and dimethyl sulfoxide (DMSO) but is insoluble in water [16]. Curcumin has a molecular weight of 368.38 g/mol and a melting point of about 183°C. Because of its long conjugated structure, which also adds to its antioxidant qualities, it shows considerable absorbance in the visible area (λmax = 420–430 nm). While curcumin is stable in acidic environments, it breaks down quickly in alkaline or light-exposed situations, producing compounds like vanillin and ferulic acid[17]. b. Chemical Structure and Composition Curcumin's molecular formula is C₂₁H₂₂O₄, making it a diferuloylmethane. It is a member of the diarylheptanoid class of natural compounds and can exist in two tautomeric forms, keto and enol, depending on the pH and polarity of the solvent. The stability and metal-chelating properties of the molecule are attributed to the enol form, which is predominant in organic solvents [18]. Curcumin's structure is made up of two o-methoxy phenolic rings joined by a seven-carbon linker that contains an α,β-unsaturated β-diketone moiety. The conjugated system enhances its electrical resonance and reactivity with biomolecules, while the presence of phenolic hydroxyl and methoxy groups confers antioxidant and free-radical scavenging properties [19]. c. Biosynthesis of Curcumin Curcuma longa uses the phenylpropanoid pathway, which starts with the amino acid phenylalanine, to produce curcumin[20,21]. The following are the crucial steps: i. Phenylalanine Phenylalanine is converted into cinnamic acid by ammonia-lyase (PAL). ii. Cinnamic acid is hydroxylated by cinnamate-4-hydroxylase (C4H) to produce p-coumaric acid. iii. P-coumaric acid is converted to p-coumaroyl-CoA by 4-Coumarate-CoA Ligase (4CL). iv. Curcumin is created when curcumin synthase (CURS) or diketide-CoA synthase (DCS) condenses two molecules of p-coumaroyl-CoA with one molecule of malonyl-CoA [22]. International Journal of Pharmaceutical Science and Health Care Volume 15, Number 6, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17602078 Original Article ©2025 RS Publication, rsp[email protected]m 61 Figure 1. Schematic representation of the structure and biosynthetic pathway of curcumin [23,24, 25]. 3. Mechanisms of Anticancer Action Curcumin targets several signalling pathways that are essential for the development, propagation, and spread of cancer through a number of molecular processes. Curcumin exhibits a pleiotropic impact, interacting with multiple molecular targets at once, in contrast to traditional chemotherapy medicines that act on a single target. Combating complex disorders like cancer, which include several dysregulated pathways, is thought to benefit from this multitargeted approach[26]. Curcumin's capacity to cause malignant cells to undergo apoptosis is one of its main anticancer methods. By upregulating pro-apoptotic proteins like Bax, Bak, and caspases and downregulating anti-apoptotic proteins like Bcl-2 and Bcl-xL, curcumin stimulates both internal (mitochondrial) and extrinsic (death receptor-mediated) apoptotic pathways. Additionally, it depolarises the mitochondrial membrane, which releases cytochrome c and activates caspase-9 and caspase-3, causing programmed cell death[27]. The suppression of cell growth is another important process. Important proliferative signalling cascades, such as the Wnt/β-catenin, MAPK/ERK, and PI3K/Akt/mTOR pathways, are suppressed by curcumin. Curcumin decreases tumorigenic potential and stops the unchecked proliferation of cancer cells by downregulating certain oncogenic pathways[28]. Additionally, transcription factors that are essential for tumour survival are disrupted by curcumin. Notably, it suppresses nuclear factor-kappa B (NF-κB), a transcription factor that controls genes linked to angiogenesis, metastasis, inflammation, and cell proliferation. Curcumin inhibits the expression of cyclin D1, COX-2, MMPs, and VEGF via blocking NF-κB activation, which lowers tumour development and metastasis. Curcumin also suppresses signal transducer and activator of transcription 3 (STAT3), which is essential for immune evasion and cancer cell survival[29]. International Journal of Pharmaceutical Science and Health Care Volume 15, Number 6, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17602078 Original Article ©2025 RS Publication, rsp[email protected]m 62 Another important element in the development of cancer is oxidative stress. Because of its high antioxidant properties, curcumin can neutralise reactive nitrogen species (RNS) and reactive oxygen species (ROS), preventing oxidative damage to cellular proteins and DNA. It contributes to cellular homeostasis by increasing the activity of antioxidant enzymes such as glutathione peroxidase, catalase, and superoxide dismutase (SOD)[30]. Additionally, curcumin affects DNA methylation, histone acetylation, and microRNA expression to modify epigenetic pathways. Curcumin's therapeutic potential is further enhanced by these epigenetic changes, which can correct aberrant gene silencing or activation observed in cancer[31]. 4. Effects on Specific Cancer Types a. Breast Cancer Curcumin's potential for treating and preventing breast cancer has been thoroughly investigated. It targets the HER2, ERK, and NF-κB pathways to decrease metastasis, induce apoptosis, and inhibit cell proliferation. Curcumin increases chemosensitivity to drugs like paclitaxel and doxorubicin by downregulating STAT3 and β-catenin in triple-negative breast tumours and interfering with oestrogen signalling in oestrogen receptor-positive (ER+) malignancies[32]. b. Colorectal Cancer Curcumin serves as a therapeutic and chemopreventive agent for colorectal cancer (CRC). By inhibiting the expression of COX-2 and iNOS, it prevents colon cancer cells from proliferating and lessens the carcinogenesis caused by inflammation. Research indicates that curcumin can prevent tumour development in APC^Min mice by blocking the Wnt/β-catenin pathway. It also reduces chemotherapy-induced toxicity by increasing the efficacy of oxaliplatin and 5fluorouracil[33]. c. Lung Cancer Curcumin inhibits proliferation and induces apoptosis in lung cancer by modulating the PI3K/Akt and NF-κB pathways. It limits metastasis by decreasing the epithelial-mesenchymal transition (EMT). Additionally, curcumin works in concert with gemcitabine and cisplatin to enhance their therapeutic efficacy while reducing oxidative damage to healthy tissues[34]. d. Prostate Cancer Curcumin reduces the survival of tumour cells in prostate cancer by suppressing the Akt and NFκB pathways and downregulating the expression of androgen receptors. It may be used as an adjuvant in androgen deprivation therapy because it suppresses VEGF expression, which decreases angiogenesis, and modifies the levels of prostate-specific antigen (PSA)[35]. International Journal of Pharmaceutical Science and Health Care Volume 15, Number 6, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17602078 Original Article ©2025 RS Publication, rsp[email protected]m 63 e. Pancreatic Cancer Curcumin targets the NF-κB, STAT3, and Notch signalling pathways to increase apoptosis and limit the growth of pancreatic cancer cells. Preclinical models have demonstrated its capacity to decrease chemoresistance and make cancer cells more sensitive to gemcitabine[36]. f. Leukemia and Lymphoma In leukaemia cells, curcumin causes cell cycle arrest in the G2/M phase and initiates apoptosis by activating caspase. Curcumin inhibits lymphoma growth by downregulating Bcl-2 and modifying JAK/STAT signalling. Its effectiveness in treating haematological malignancies is further increased by its capacity to lower inflammation and oxidative stress[37]. 5. Curcumin and Cancer-Associated Complications Curcumin has preventive effects against several problems related to cancer progression and therapy, in addition to its direct anticancer activity[38]. a. Inflammation One of the main causes of tumour growth and metastasis is persistent inflammation. The potent anti-inflammatory effects of curcumin are mediated by the inhibition of NF-κB, COX-2, TNF-α, and IL-6. It makes the tumour microenvironment less conducive to the recruitment of inflammatory cells, which hinders the advancement of cancer[39]. b. Oxidative Stress High ROS levels are frequently produced by cancer cells, which can result in genomic instability and DNA alterations. By scavenging free radicals and boosting antioxidant defences, curcumin reverses this. It increases the transcription of cytoprotective genes involved in detoxification and the oxidative stress response via modifying Nrf2 signalling[40]. c. Cachexia and Fatigue In patients with advanced cancer, cancer cachexia is a crippling illness marked by extreme weight loss and muscle atrophy. By altering the ubiquitin-proteasome system and lowering inflammatory cytokines like TNF-α and IL-1β, curcumin has demonstrated promise in decreasing cachexia. Its antioxidant properties also enhance quality of life and fight cancer-related weariness[41]. d. Cardiovascular and Hepatic Complications Hepatotoxicity and cardiotoxicity are side effects of several chemotherapy medications. By lowering lipid peroxidation, boosting antioxidant enzyme activity, and stabilising cellular membranes, curcumin provides protection. Curcumin can lessen cisplatin-induced liver toxicity International Journal of Pharmaceutical Science and Health Care Volume 15, Number 6, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17602078 Original Article ©2025 RS Publication, rsp[email protected]m 64 and doxorubicin-induced heart damage without compromising anticancer activity, according to preclinical research[42]. 6. Bioavailability and Formulation Strategies Curcumin's poor absorption limits its clinical success despite its amazing pharmacological potential. It has quick metabolism, limited water solubility, and systemic elimination. Curcumin is extensively first-pass metabolised in the liver and intestines after oral treatment, resulting in conjugates of glucuronide and sulphate that have less biological activity[43]. Many techniques have been devised to increase curcumin's solubility, stability, and absorption in order to get around these restrictions[44]. a. Nanoparticle Formulations By preventing degradation and promoting cellular uptake, curcumin's encapsulation in nanoparticles increases its bioavailability. In preclinical cancer models, polymeric nanoparticles, solid lipid nanoparticles, and nanoemulsions have shown enhanced therapeutic efficacy and better pharmacokinetic characteristics[45]. b. Liposomal Curcumin Curcumin's systemic circulation duration and tissue accumulation are prolonged by liposomal preparations. In animal experiments, liposomal curcumin has demonstrated greater tumour suppression and increased cytotoxic effects against a variety of cancer cell lines[46]. c. Phytosome Complexes Curcumin's absorption through the intestinal wall is enhanced via curcumin-phospholipid (phytosome) complexes, leading to increased plasma concentrations. When compared to unformulated curcumin, phytosomal curcumin formulations have shown better anti-inflammatory and antioxidant properties[47]. d. Curcumin Analogs and Derivatives More powerful and stable analogues of curcumin, such as EF24, GO-Y030, and CDF (curcumin difluorinated derivative), have been created through structural alteration of curcumin. These analogues have higher anticancer potency, improved cellular absorption, and increased metabolic stability[48]. e. Combination with Bioenhancers By preventing glucuronidation, co-administration of bioenhancers like piperine (found in black pepper) greatly increases curcumin's bioavailability. Piperine is a useful strategy in dietary International Journal of Pharmaceutical Science and Health Care Volume 15, Number 6, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17602078 Original Article ©2025 RS Publication, rsp[email protected]m 65 supplements and therapeutic formulations since it can raise the serum concentration of curcumin by up to 2000% [49]. 7. Toxicity and Safety Profile The U.S. Food and Drug Administration (FDA) has classified curcumin as generally recognised as safe (GRAS), and even at high dosages, it shows little harm. Oral dosages up to 8 g/day are well-tolerated without major side effects, according to preclinical research. At very high dosages, nausea and gastrointestinal distress are reported moderate adverse effects[50]. Curcumin did not show any genotoxic or mutagenic effects in animal experiments. Its natural origin and safety profile make it a desirable supplement to traditional treatments. However, because curcumin might increase bile production, patients with gallstones or bile duct obstruction should exercise caution[51]. 8. Future Perspectives and Clinical Implications Curcumin's anticancer activity is supported by a wealth of in vitro and in vivo data, but clinical validation is still a significant obstacle. Curcumin has shown promise in lowering tumour indicators, enhancing patient quality of life, and reducing treatment-related side effects in numerous clinical trials. For example, curcumin administration has been linked to lower COX-2 expression and fewer polyps in patients with colorectal cancer[52]. However, curcumin's translation from bench to bedside has been hampered by variations in dosage, formulation, and pharmacokinetics. In order to attain constant bioavailability, future research should concentrate on creating standardised formulations with optimised delivery mechanisms. Additionally, curcumin may have synergistic benefits with current immunotherapies or chemotherapy drugs, improving therapeutic results while lowering toxicity[53]. Formulations based on nanotechnology, such as stimuli-responsive carriers and targeted nanoparticles, show promise for improving curcumin delivery to tumour tissues. Furthermore, investigating curcumin's impact on immune response, tumour microenvironment, and epigenetic regulation may open up new therapeutic options for cancer[54]. 9. Summary The main bioactive component of Curcuma longa, or turmeric, is curcumin, which has attracted a lot of interest due to its strong anticancer and medicinal qualities[55]. It demonstrates a variety of biological actions, such as pro-apoptotic, anti-inflammatory, antioxidant, and antiproliferative properties[56]. Curcumin modulates transcription factors including NF-κB, STAT3, and AP-1 to target many molecular pathways involved in cancer initiation, growth, angiogenesis, and metastasis. Additionally, it lessens the toxicity of traditional chemotherapy and radiation therapies while increasing their effectiveness. Additionally, curcumin reduces oxidative stress, International Journal of Pharmaceutical Science and Health Care Volume 15, Number 6, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17602078 Original Article ©2025 RS Publication, rsp[email protected]m 66 inflammation, and cachexia—complications linked to cancer. Curcumin has an impressive pharmacological profile, but its quick metabolism and low bioavailability restrict its use in clinical settings[57,58]. Novel formulations, including liposomes, phytosomes, and nanoparticles, have been created to improve its therapeutic efficacy in order to overcome these obstacles. All things considered, curcumin is a naturally occurring, safe, and promising substance with great promise as an adjuvant in integrative cancer therapy [59,60]. 10. Conclusion Curcumin is a powerful and adaptable natural substance that holds great potential for both preventing and treating cancer and its related consequences. Its wide therapeutic potential is supported by its capacity to affect several signalling pathways as well as its anti-inflammatory and antioxidant properties. Even if there are still issues with bioavailability, developments in formulation science and molecular research are improving its clinical usefulness. Curcumin may become a key component of integrative cancer therapy with further clinical validation efforts, providing a secure and efficient supplement to current therapeutic approaches. 11. Acknowledgement We would like to acknowledge Department of Pharmacy, Sanaka Educational Trust’s Group of Institutions, Maulana Abul Kalam Azad University of Technology, West Bengal, India for encouragement and support. • Competing Interests: Nil References 1) Jyotirmayee B, Mahalik G. 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