Enhanced anticancer potential of Punica granatum fruit extract in combination with Pheophorbide – a mediated photodynamic therapy on MCF-7 breast cancer cells.

Researchers: Nosipho Fakudze, Paromita Sarbadhikary, Heidi Abrahamse & Blassan P. George University of Johannesburg.

July 2025.

What Is The Study About?

Combination therapy refers to the simultaneous administration of several therapeutic medications and treatment procedures with diverse biochemical and molecular targets and mechanisms of action. This is now used to treat a range of cancers. The search for less toxic natural alternatives has gained importance, which has led researchers’ interest in phytotherapy-based combination therapies. Punica granatum leaf, fruit, seed, and peel extracts, like many other medicinal plants, contains a high concentration of phytochemicals like tannins, anthocyanidins, phenolics, and have shown to be effective in cancer treatment. In this study, the anticancer potentials of P. granatum extract were evaluated in combination with a chlorophyll derivative photosensitizer, pheophorbide-a mediated photodynamic therapy (PDT) against MCF-7, a human breast cancer cell line. The findings suggest that a combination of phytocompound-based therapeutic modalities with different mechanisms of action has the potential to significantly improve cancer treatment efficacy when compared to single-agent therapy.

Why Is This Important?

Cancer is considered one of the most serious diseases globally and new and advanced treatment modalities are continuously being investigated. According to the reports (global cancer statistics, GLOBOCAN), the sharp rise in cancer cases globally, is putting an unprecedented level of emotional, physical, and financial pressure on patients, their families, healthcare systems, and communities. In middle- and low-income countries, many cancer patients are not receiving reliable treatment because of the unpreparedness of healthcare systems to handle the daily increase in cancer incidence. Current issues associated with conventional treatments such as surgery, chemotherapy, and radiotherapy include pulmonary toxicity, cancer-related fatigue, peripheral neuropathy, cardiotoxicity, cognitive, gastrointestinal, and musculoskeletal impairments. As a result, a relatively safer and cost-effective treatment strategy is critical to address the alarming global rise in cancer cases as well as the major limitations of current treatments options. A wide range of medicinal plants are being studied for their phytotherapeutic properties due to their low-induced side effects and inherent sustainability. Natural products have recently gained the interest of researchers due to their multitargeted mechanisms of action, lower systemic toxicity, and potential to overcome drug resistance. This can lessen side effects and improve the efficacy of cancer treatments. Over 65% of small-molecule anticancer drugs approved between 1981 and 2019 are derived from or inspired by natural sources, while some other phytocompounds are currently in Phase 2 or 3 clinical trials for various cancers.

What We Know…

Herbal extracts and medicinal plants were used to treat several different human ailments for many years, including digestive disorders, respiratory conditions, skin problems, infectious diseases, inflammation, cardiovascular conditions, neurological conditions, metabolic disorders, immune booters and reproductive health. Natural compounds have been given a lot of attention as cancer-preventive and therapeutic agents since several bioactive phytocompounds have been found to have anticancer properties and many of them have even received clinical approval. Natural product botanicals (0.4%), natural product derivatives (29.7%), and unaltered natural products (18.9%) account for the 247 antitumor drugs approved up to 2019; this demonstrates the significant probability for anticancer phytochemicals for future phytotherapies for cancer. Many patients employ natural or plant-based remedies in conjunction to traditional anticancer therapies to decrease the chemotherapy side effects, increase immune system function, manage illness symptoms, and promote overall health.

Types of Therapies…

Due to the diverse nature of cancer and the involvement of multiple targets and cancer-causing pathways, monotherapy has limited effectiveness in the treatment and prevention of cancer. Combination therapy is now frequently used to treat various types of cancer. Using multiple drugs or therapies has the significant advantage of lowering the drug doses. The combination of one or more natural compounds for cancer prevention and treatment is of great interest because this treatment regimen overcomes the use of chemical drugs.

Photodynamic Therapy (PDT) is a potentially effective clinically approved therapeutic alternative for the treatment of cancer. PDT offers several advantages over other conventional treatment modalities, including minimal systemic toxicity, the ability to target and eradicate specific tumours, and the ability to be used either in isolation or addition to alternative therapeutic approaches.

The Future of Cancer Treatments?

Caution must be taken when interpreting these findings, as several bioactive metabolites, which are often produced by intestinal or hepatic metabolism, are not 100% viable and there are certain areas that need much more investigation. 

Also, a direct comparison with conventional chemotherapeutic treatments was not included, the literature indicates that these chemotherapeutic drugs, used as the first line of treatment for breast cancer, despite their high effectiveness, are frequently linked to dose-limiting toxicities and multidrug resistance. On the other hand, a combination of phytochemical-based treatment as used in this study, provides a more effective treatment strategy. Even though this is a preliminary study, the results demonstrate the therapeutic value of combining plant-based bioactive compounds with PDT as a complementary or alternative strategy, particularly when traditional treatments show limited responses or have serious adverse effects.