Apigenin in cancer therapy: anti-cancer effects and mechanisms of action

In the scientific paper Apigenin in Cancer Therapy: Anti-cancer Effects and Mechanisms of Action, Yan et al. explore the potential of apigenin, a naturally occurring flavonoid found in many fruits, vegetables, and medicinal herbs, as a treatment for cancer. The authors review extensive research on how apigenin can inhibit cancer cell growth, promote apoptosis (programmed cell death), and prevent metastasis. With its low toxicity compared to traditional chemotherapy, apigenin also shows promise in boosting the immune response to cancer cells and targeting cancer stem cells. The paper highlights apigenin's ability to act on multiple biological pathways, making it a compelling candidate for future cancer therapies.

Apigenin is a flavonoid, a type of natural compound found in many fruits, vegetables, and herbs such as parsley, apples, and chamomile tea. This compound has been used for centuries in traditional medicine because of its various health benefits, including its anti-inflammatory, antioxidant, antibacterial, and antiviral properties. More recently, researchers have discovered apigenin's potential in fighting cancer.

Cancer is the second leading cause of death worldwide, and current treatments like chemotherapy can have serious side effects, including damage to healthy cells and the development of drug resistance. Apigenin, however, offers a promising alternative. It not only fights cancer with fewer side effects but also has been found to be effective against many types of cancers, such as colorectal, breast, lung, prostate, and liver cancers. According to the study , "apigenin suppresses cancer cell proliferation, migration, and invasion" through multiple pathways, making it a versatile anti-cancer agent.

The researchers conducted a comprehensive review of studies focusing on apigenin's impact on cancer cells. These studies included laboratory experiments (in vitro) where cancer cells were treated with apigenin and animal studies (in vivo).

The goal was to analyze how apigenin affects cancer at the molecular level, particularly by examining how it influences key signaling pathways involved in cancer cell survival, growth, and spread. These pathways include PI3K/AKT, MAPK/ERK, and JAK/STAT, which are critical for the development and progression of cancer. The study also reviewed how apigenin works in combination with other therapies to enhance its anti-cancer effects.

One of the most essential effects of apigenin is its ability to slow down or stop cancer cells from growing. Cancer cells grow uncontrollably, but apigenin can block this by arresting the cell cycle at different stages, such as the G2/M or G0/G1 phases. This process freezes the cancer cells, preventing them from dividing and multiplying. For example, in colorectal cancer cells, apigenin "suppressed the expression of cyclin B1 and Cdc2, two proteins that are crucial for cell division." This means that apigenin stops cancer cells from completing their life cycle, which could slow or halt tumor growth.

Apigenin is also effective at inducing apoptosis or programmed cell death. Normally, cancer cells avoid dying, which allows them to grow uncontrollably. Apigenin forces them to undergo apoptosis by acting on both the intrinsic and extrinsic pathways, which are two main ways that cells self-destruct. The study notes that in prostate cancer cells, apigenin "caused a reduction in Bcl-2, a protein that prevents apoptosis while increasing Bax, a protein that promotes cell death." This balance is key to encouraging cancer cells to die off naturally.

Another mechanism by which apigenin works is through autophagy, a process where cells break down and recycle their own components. While autophagy can sometimes help cancer cells survive by cleaning out damaged parts, it leads to cell death in some cancers. For example, in breast cancer cells, apigenin triggered both apoptosis and autophagy, with the researchers explaining that "the accumulation of LC3-II, a marker for autophagy, was seen after apigenin treatment." This dual action helps make apigenin a powerful agent against cancer.

Apigenin has also been shown to reduce the ability of cancer cells to migrate and invade other tissues, which is crucial because cancer spreads through the body by metastasis. For instance, apigenin suppressed cell migration in lung cancer cells by "inhibiting the phosphorylation of AKT, which is necessary for cell movement and invasion." Similarly, in studies on melanoma (skin cancer), apigenin decreased the levels of proteins like MMP-9, which cancer cells use to break through tissue barriers and spread to other parts of the body.

Apigenin can enhance the body's natural immune response to cancer cells. One way it does this is by inhibiting the PD1/PD-L1 interaction, which cancer cells use to hide from immune cells. By blocking this pathway, apigenin allows immune cells to recognize and attack the cancer. In a study on breast cancer, apigenin "downregulated the expression of PD-L1 in response to interferon-gamma," which would otherwise suppress the immune system's ability to fight cancer. This shows that apigenin can help the immune system better target cancer cells.

Apigenin also targets cancer stem cells, which are a small group of cells within a tumor that can lead to resistance to chemotherapy and cancer recurrence. In head and neck cancer, apigenin "significantly reduced the levels of stem cell markers like CD44 and NANOG," which are essential for cancer stem cells to renew themselves. By weakening these stem cells, apigenin may help reduce the risk of cancer returning after treatment.

The study highlights apigenin's potential as a multi-faceted cancer treatment. Its ability to stop cancer cells from growing, cause them to self-destruct, prevent them from spreading, and enhance the immune response makes it an exciting prospect for cancer therapy. Apigenin also stands out because it works through several important biological pathways simultaneously. It affects the PI3K/AKT, MAPK/ERK, and JAK/STAT pathways, which are often overactive in cancer cells. By targeting these pathways, apigenin blocks cancer's ability to survive and spread.

Furthermore, apigenin has low toxicity, meaning it doesn't harm healthy cells as much as traditional chemotherapy drugs do. This makes it a safer option for long-term use or for patients who need treatments that are less harmful to their overall health. The study indicates that apigenin's effects are "remarkable in terms of its low toxicity and non-mutagenic properties." This means it has the potential to be used not only as a supplement to traditional cancer treatments but also as part of a strategy to prevent cancer from developing in the first place.

Apigenin shows great promise as a natural compound that could significantly improve cancer therapy. It has been found to slow cancer growth, induce cancer cell death, prevent cancer from spreading, and boost the body's immune response to cancer. Apigenin stands out because it works through multiple pathways, allowing it to attack cancer from different angles.

In addition, its low toxicity makes it a safer alternative to traditional chemotherapy, which often comes with severe side effects. This scientific paper suggests that apigenin could one day be used as a cancer prevention supplement and companion treatment alongside other cancer therapies. As research continues, apigenin may become a key player in helping more people fight cancer with fewer side effects.