Skin cancer remains one of the most preventable malignancies. Yet its incidence rates continue to rise despite research, policy changes, and decades of public health initiatives focused on behavioral modification, including sunscreen campaigns, tanning bed legislation, and education on UV exposure.^1–4 Despite all these educational efforts in the United States, the number of people diagnosed with skin cancer is higher than the combination of all other cancers diagnosed annually.^3,4 Melanoma affects around 230,000 annually, while non-melanoma skin cancer (NMSC) exceeds 5.4 million cases yearly.^3,4 This trend has significant clinical and economic implications, as treatment costs for melanoma and NMSC were estimated to be around eight billion dollars.⁴ Skin cancer has become a significant burden to the health care system.

Ultraviolet radiation (UV) is a known primary environmental driver for developing cutaneous malignancy and is responsible for upwards of 80-90 percent of all skin cancer cases.^2,5–8 While there are three distinct wavelengths of UV radiation categorized into A, B, and C, both UVA and UVB are known to be involved in carcinogenesis, albeit their mechanisms differ. UVA, known to induce indirect oxidative stress and single-strand DNA breaks, whereas UVB causes direct DNA damage, leading to mutations critical in skin cancer development, highlighting the importance of understanding the distinct effects of UV radiation.² Chronic unprotected UV exposure leads to cumulative molecular damage, resulting in promoting tumor development and progression.

While numerous sun-protective strategies are being implemented, they focus on minimizing UV exposure through sunscreen use, protective clothing, and other behavioral modifications. Despite public awareness efforts, the rise in incidence rates suggests that other mechanisms are at play. These efforts directed at UV protection serve as important modifiers but nutraceutical and nutritional interventions may enhance the skin’s intrinsic capacity to neutralize UV-induced damage. Currently, this represents a complementary and understudied strategy for photoprotection.

The current literature supports the hypothesis that supplementing with anti-oxidants may bolster the skin’s natural defense mechanisms by decreasing reactive oxygen species (ROS), limiting DNA damage, and enhancing the skin’s immune defenses and repair. This review explores the potential adjuvant use of Cyano-Phycocyanin (C-PC) to reduce ROS and DNA damage and enhance the skin’s natural immune response and repair mechanisms, with the potential to decrease skin cancer prevalence.

There has been a recent surge of interest and research in algal bioactives as potential anti-oxidants that may help mitigate UVR-induced damage. C-PC is a phycobiliprotein extracted from Arthrospira platensis (AP) or Spirulina.⁹ Spirulina, a nutrient-dense blue-green non-toxic algae, is considered the “best food for the future” or a superfood.^9–11 More specifically, Spirulina has been utilized as a dietary supplement in food due to its high protein value (60-70%).^10,11 The Food and Drug Administration identifies Spirulina as safe for human consumption.^9,10 In addition to its high protein content (TABLE 1), it is also rich in minerals such as iron, magnesium, potassium and trace elements like zinc; vitamins including B1, B2, B3, E and beta-carotene; anti-oxidants such as phycocyanin, chlorophyll, betacarotene, and superoxide dismutase (SOD); fatty acids including gamma-linolenic acid (GLA) and omega6 fatty acid, and polysaccharides like immulina. These confer potential medicinal benefits on Spirulina, including anti-oxidant and anti-inflammatory properties, anti-glycation effects, immune support, cardiovascular health benefits, beneficial effects on insulin sensitivity and blood glucose control, antimicrobial properties, promotion of detoxification, and skin health benefits, including wound healing.^9,10

335602 Table 1.

C-PC, a pigment-protein complex, has a vibrant blue color due to its bilin chromophores, which make up approximately 10-20% of Spirulina’s total biomass.¹² C-PC has been extensively studied for its potential therapeutic benefits, including anti-oxidant, anti-inflammatory, immune-modulatory, anti-cancer, wound-healing, and other health-promoting properties, such as its ability to reduce UVR-induced skin damage.^9,11,13 Specifically, C-PC has been found to play a potential role in preventing skin cancer by either reducing UVR damage or by promoting skin repair.⁹ One of the mechanisms involved in UV-protection by C-PC is its ability to directly scavenge free radicals, including O^2•−, OH-, and H₂O₂, preventing oxidative stress.⁹ In addition, C-PC enhances the activity of endogenous anti-oxidant enzymes such as SOD, catalase (CAT), and glutathione peroxidase (GPx),^9–11,14 and downregulates pro-oxidant enzymes such as nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase.¹⁵

Humans have evolved multiple endogenous anti-oxidant defenses, such as SOD, to protect essential biomolecules against damage caused by ROS generated endogenously (eg, during cellular metabolism, inflammation, aging, and cancer) and exogenously (eg, UVR, pollution, certain foods, and drugs).¹⁶ Anti-oxidants reduce, repair, and even prevent ROS-induced damage to specific biomolecules such as proteins, nucleic acids, and lipids.¹⁶ It has three known modes of action: (i) direct scavengers of already formed ROS; (ii) inhibition of the formation of ROS via their cellular source; and (iii) removing or repairing damages or modifications as a result of ROS.¹⁷ Though ROS generation can be beneficial to signal molecules in metabolism at low levels, the excess stimulation of ROS exogenously and endogenously can overwhelm normal tissue or cellular defenses, leading to oxidative stress and biological damage.^2,18 C-PC, as an anti-oxidant, can potentially target excess oxidative stress and its damaging effects at the cellular level by stabilizing ROS radicals/non-radicals to prevent damage.^17,18 This review will explore the potential of C-PC, with its strong anti-oxidant and anti-inflammatory properties, to help protect and repair the skin from UVR-induced damage.

PubMed, ClinicalKey, and the Cochrane Library were used to conduct a literature search, as they successfully identified C-PC and other terms required for the study. Other databases, such as UpToDate and Clinical Pharmacology, did not include any findings on C-PC and were therefore not used. Initial search terms included Spirulina, phycocyanin, anti-oxidant, and skin cancer prevention. Additional search terms included C-PC, oxidative stress, free-radical damage, anti-inflammatory effects, immunomodulation, anti-cancer effects, and UVR-induced DNA damage. The search was further narrowed to 2019-2025; however, research beyond this period was considered and used for foundational work on the topic. Articles prioritized using refined terms on the anti-cancer properties of C-PC, the impact of oxidative stress, and the proposed cellular mechanisms of action of C-PC were identified, yielding a total of twenty manuscripts. Research on C-PC included both in vivo and in vitro studies conducted in multiple countries, including the US, Switzerland, China, India, Cuba, Brazil, Korea, Taiwan, and Japan. All in vitro and in vivo studies, except the Japanese wound-healing study, used analysis of variance (ANOVA), with p < 0.05 considered statistically significant. The Japanese study analyzed the data using Student’s t-test, with p < 0.05 considered statistically significant. We identified two small human clinical studies (in Japan and the US) focused on the nutraceutical effects of C-PC as an anti-oxidant. The American observational study (n = 4; two females and two males between the ages of 30 and 60 years old) examined the use of C-PC that was patent pending. The Japanese clinical study was a randomized, double-blind, placebo-controlled, parallel-group comparison (n = 96, females between 20 and 65 years old).

Healthy skin function depends on protection against external agents, including UVR, microorganisms, pollution, allergens, and other environmental factors, as well as on maintaining internal homeostasis and adequate hydration to sustain an intact epidermal barrier and optimal health.^40,41 Y. Imai et al reported in a randomized, double-blind, placebo-controlled, parallel-group trial that C-PC improved skin barrier function by reducing transepidermal water loss (TEWL).⁴¹ The authors used 410 mg of phycocyanin (C-PC 300 mg, allophycocyanin 110 mg) once daily for 8 weeks, resulting in improved skin moisture and elasticity measured by visual analog scale (VAS).⁴¹ This data may support the hypothesis that C-PC supplementation helps skin to become more resilient and healthier, and therefore may play a role in preventing skin cancer development. A healthy skin barrier is essential for protecting the body from environmental stressors, such as UVR. With chronic exposure, the skin’s molecular pathways are adversely affected, leading to photoaging.⁴² In addition, C-PC’s capacity to suppress specific cell-cycle phases, modulate the cellular redox state, regulate proliferation, and induce apoptosis and necrosis may play a significant role in its anti-tumor activity. In a murine model, the authors showed that topical application of C-PC downregulated TPA (12-0-tetradecanyol-phorbol-13-acetate)-induced ODC (ornithine decarboxylase). ODC plays a role in epidermal tumorigenesis and is induced by UVB and hormones, and is strongly expressed in SCC and BCC.⁴³

A patent filed by L. Lerer in the US for the purification of C-PC and its applications reported the use of a 250 mg lyophilized powder administered daily to an undisclosed number of fair-skinned subjects, who reported reduced sunburn potential via self-reported observation.⁴⁴ A case study (n = 4, Fitzpatrick phototypes I and II) showed a protective effect of C-PC supplementation (250 mg qd for five days) to targeted narrow-band UVB skin damage (forearm).⁴⁴ Participants served as their own controls and experienced decreased skin peeling, pain, and sensitivity, and rapid skin recovery after consuming lyophilized C-PC supplementation.⁴⁴

C-PC in vitro and animal study data have shown anti-oxidant, anti-inflammatory, photoprotective, and antitumorigenic effects. However, clinical trials in humans are lacking, whereas preclinical studies provide a foundation for C-PC’s potential protective role against UVB-induced skin damage. Addressing this gap, a 2025 systematic review and meta-analysis of 22 randomized clinical trials (n = 5,385) supported the systemic efficacy of spirulina supplementation. The study demonstrated reductions in key inflammatory markers, including CRP, IL-6, and TNF-α, alongside a marked decrease in oxidative stress markers like MDA and an increase in total antioxidant capacity (TAC) in humans.⁴⁵ The absence of clinical trials evaluating C-PC for UVB-induced skin damage in humans can be attributed to several key factors. Primarily, C-PC’s high molecular weight poses significant bioavailability challenges, limiting its skin penetration and systemic absorption and complicating the development of effective topical or oral formulations for clinical use. While preclinical studies have demonstrated C-PC’s potent anti-oxidant and anti-inflammatory effects, the transition to human trials is hindered by the need for advanced delivery systems, such as solid-in-oil nanodispersions, which remain in early development. However, recent advances in C-PC delivery, reported by D. Galinyte et al have demonstrated delivery systems with enriched transfersomes that enable epidermal delivery of C-PC while maintaining stability for up to eight months, providing a viable alternative to solid-in-oil nanodispersions.⁴⁶ Additionally, research on C-PC has largely focused on its systemic benefits (eg, anti-cancer and anti-inflammatory properties) and preclinical photoprotection models, with less emphasis on dermatological applications in humans. Regulatory and funding barriers further delay clinical trials, as natural compounds like C-PC require substantial investment and rigorous safety validation to meet cosmeceutical or therapeutic standards. Limited awareness of C-PC’s photoprotective potential in dermatology may contribute to its underexploitation in clinical settings, despite promising preclinical data. Lastly, standardization of the C-PC dose used topically for anti-aging, photoprotective, wound-healing, or anti-inflammatory benefits requires further investigation. Currently available data provide only in vitro and animal studies that suggest doses for specific benefits (Table 2). C-PC’s mechanism of action as a phycobiliprotein and other bioactive molecules contributes to the cellular level’s enzymatic and non-enzymatic anti-oxidant defense against UVR, microorganisms, and pollution, keeping skin healthy, as seen in Figure 2.

Annual skin examinations for high-risk patients, education, encouragement of monthly self-exams, and the use of protective measures such as sunscreen, UV-protective clothing, and other tools are often recommended by dermatology providers. Protecting the skin’s external surface is necessary, but targeting the underlying cellular mechanisms can further reduce the incidence of skin cancer. While these protective measures are essential, growing evidence indicates that oxidative stress and cellular inflammation contribute to UVR-induced skin damage. This is supported by recent large-scale human evidence, including a 2025 meta-analysis of twenty-two clinical trials (n = 5,385) that confirmed that supplementation with Spirulina significantly reduces systemic inflammatory markers, such as IL-6 and CRP, while enhancing total antioxidant capacity in humans.⁴⁵

Antioxidant properties are primarily found in C-PC, and its functional properties have been studied, including radical scavenging, antioxidant, anti-inflammatory, antimicrobial, anti-cancer, and wound-healing activities.^10,47 Topical applications on human skin, particularly dermal keratinocytes, are promising, as studies have demonstrated that ROS production by UVB induction has been reduced by over 50%.⁴⁷ In vitro studies have shown the potential to decrease DNA fragmentation in UVB-irradiated cells treated with C-PC, decrease UVB-induced production of ROS over 50%, decrease levels of MMP-1 and MMP-9, and tyrosinase activity, and show a pro-apoptotic influence on different cancer lines.^10,18,30,48 New quantitative data further validate these mechanisms, demonstrating that C-PC can reduce IL-1β gene expression by over 70% and nitric oxide secretion by 91% in stimulated human cells while maintaining near-perfect cell viability.²⁹ In vivo studies showing that C-PC increases SOD2 activity through activation of Nrf2 signaling, enhances free-radical scavenging and reduces oxidative stress in cells, and promotes mediators and fibroblast proliferation and migration for tissue regeneration collectively suggest a likely contribution to its anti-oxidant potential and dermal wound healing.^{10,23,24,38,39}

The clinical utility of these findings is supported by the recent development of enriched transferosomes, which have been shown to deliver C-PC to the epidermis and remain stable for up to eight months.⁴⁶ The mechanism of action of C-PC and its potent anti-oxidant capacity are shown to slow skin aging, resulting in fewer wrinkles, making it a potential anti-aging nutraceutical and UVR adjunct protectant.^47,49 Finally, C-PC may serve as a potential adjuvant cancer treatment due to its well-studied effects on cancer cells in vitro using human cell cultures.¹⁰ It shows a pro-apoptotic influence on different cancer lines such as breast, colorectal, lung, squamous cell, melanoma, and leukemia.¹⁰ C-PC has also undergone numerous in vivo and in vitro anti-cancer studies and has shown significant inhibitory effects on growing cancer cells, including inhibition of DNA replication, cell cycle arrest, and apoptosis, along with low toxicity to healthy cells and minimal generation of ROS.^9,50,51 Its promising anti-cancer activity has been studied by showing C-PC inducing tumor cell autophagy and apoptosis by inhibiting the tumor cell cycle by suppressing at specified phases, modifying the redox state, and promoting genes and receptors that promote apoptosis.⁵¹

At present, clinical use of C-PC should be approached cautiously. Human data remain limited, and available studies rely on surrogate measures of skin health rather than on validated outcomes of photoprotection or skin cancer prevention. However, as patient interest in nutraceuticals and oral photoprotective strategies continues to grow, dermatology providers may benefit from understanding the existing evidence to guide informed clinical discussions, set appropriate expectations, and emphasize evidence-based sun safety practices. Worth noting: C-PC should not be viewed as a replacement for well-established sun protective behaviors, but rather as a possible adjunct to reduce UVR-induced oxidative damage. Further well-designed, placebo-controlled human trials are needed to determine whether the biological effects observed in preclinical models translate into meaningful clinical benefit. Until such data are available, C-PC remains a promising but investigational adjunct within the broader framework of UVR risk reduction.

Ultraviolet radiation protection remains the primary modifiable risk factor for cutaneous malignancies; therefore, there is a need for more effective preventive strategies beyond behavior modification. Current preclinical evidence demonstrates the anti-oxidant and anti-inflammatory benefits of C-PC on UVR-induced skin damage. The current evidence, however, is primarily derived from in vitro and animal models; as a result, human data remain limited, and the clinical effectiveness in humans has not been fully elucidated. Well-designed, placebo-controlled, randomized human trials with validated endpoints are needed to determine whether the biological effects observed in these preclinical studies translate into clinically meaningful benefits. At this time, given the available data, C-PC should be considered a promising, but still investigational, adjuvant to appropriate photoprotection.