p-coumaric acid is a phenolic acid that is abundantly found in fruits, vegetables, and Chinese herbs [23]. It contains anti-inflammatory, anti-oxidant, anti-diabetic, anti-platelet aggregation, and anti-cancer properties. To the best of existing information, the anti-cancer efficacy of p-coumaric acid is largely unknown. This is the foremost study to report the ability of p-coumaric acid in reducing the cell viability of A431 skin cancer cells. Our MTT data show that p-coumaric acid can reduce the viability in melanoma cells. This indicates a reduced mitochondrial activity after treatment with p-coumaric acid [24].
Numerous research has found a connect between diet consumption and the development of cancer [25, 26]. Therefore, it can be hypothesized that consuming diets high in fruits and vegetables on a regular basis may lower the incidence of cancer. A specific group of non-nutritive phytochemicals called phenolic compounds is found in a wide variety of foods and is thought to protect against a number of diseases, including diabetes, cancer, and a number of cardiovascular disorders [27].
When it comes to treating superficial or non-invasive skin malignancies, imiquimod is the most effective treatment; nevertheless, its effectiveness varies depending on the location and size of the tumour. For melanoma, a more dangerous type of skin cancer, it is not typically employed. Temporary redness, swelling, and localized discomfort at the application site are possible adverse effects. Thus, the development of novel pharmacological compounds for the treatment of melanoma is imperative. When opting for imiquimod treatment, patients should consult with an oncologist or dermatologist to create a personalized treatment strategy. Alternative therapies like radiation therapy or surgery may also be taken into consideration, depending on the particular conditions. Imiquimod mainly works by activating the immune system's defenses against skin tumours that are not melanoma [28, 29]. Topical medicine imiquimod is used to treat some non-melanoma skin malignancies. It is applied directly to the afflicted skin area and is administered topically as a cream. Imiquimod functions as an immune modifying medication that not only has a direct effect but also improves immune surveillance. The MTT data on p-coumaric acid and imiquimod showed similarity in their efficacy in reducing the viability of A431 cells suggest p-coumaric acid as an alternative medication instead of Imiquimod.
Several investigations have demonstrated the connection between cell cycle disruption and carcinogenesis and the development of cancer. Although the duration of the cell cycle in tumour cells is nearly identical to that in normal cells, the percentage of cells in tumour tissues that are actively dividing is significantly higher than in normal tissues [30]. The two stages of cell division, known as the mitotic phase and the interphase, make up the cell cycle. The G1, S, and G2 phases are separated from the interphase. RNA and proteins are quickly synthesized by cells in the G1 phase, providing the building blocks and energy needed for DNA replication in the S phase. DNA replication doubles the amount of DNA in cells during the S phase. One of the most important phases in the cell cycle is the change from the G1 to the S phase. Certain variables can disrupt a cell, which can impact DNA replication and result in mutations or interrupt it entirely. G2 phase cells have been prepped for the division phase. The cells proceed to the M phase for regular cell division following the interphase [31]. Control and A431 cells treated with p-Coumaric acid were analyzed for the cell cycle arrest at different phases. Cell populations were distributed in to Sub G1, G0/G1, S and G2/M phases p-coumaric acid It showed significantly decreased in Sub-G1 arrest. Overall, p-coumaric acid can block propagation of A431 cells in addition to reducing the viability.
Inhibiting the proliferation of tumour cells can also be achieved through inducing apoptosis [32]. A controlled type of cell death is called apoptosis. Genes that are activated, expressed, and regulated during apoptosis can be entered by cells on their own. Activation and regulation of the caspase family play a crucial role in the transmission of apoptotic signals, as it can be used to degrade or inactivate certain essential cellular proteins [33]. The cells were divided into quadrants that included necrosis, early and late apoptotic cells, and living cells. To assess the various forms of cellular death, a comparison was done. Although the early apoptotic cell percentage of control cells was dropped and increased in p-coumaric acid treated cells, the late apoptotic cell percentage was found as decreasing in control A431 cells and increasing in p-Coumaric acid treated A431 cells. Because of this, the number of live cells in the untreated control A431 cells was higher, which led to a drop in live cells and the induction of apoptosis in the A431 cells by p-Coumaric acid.
Mitochondrial dysfunction is a critical event that occurs in the early stages of apoptosis. Numerous chemotherapeutic drugs have been found to induce apoptosis, which is correlated with a decrease in the potential of the mitochondrial membrane. Decreased intensity of mitochondrial membrane potential measurements in p-coumaric acid-treated cells indicated mitochondrial dysfunction supports our MTT data and substantiate the mitochondrial weakening efficacy of p-coumaric acid.
ROS is involved in several metabolic processes, such as cell division and death. Generally, ROS stress has been shown to increase metabolic activity and be carcinogenic. Furthermore, by encouraging the production of more ROS via the mitochondrial respiratory chain, it preserves the cancer phenotype. But long-term exposure to high ROS levels can damage cells and induce apoptosis [34, 35]. Thus, we can use exogenous ROS-producing compounds to leverage time- and dose-dependent ROS production to induce cell death. Numerous biochemical processes, including cell division and death, are impacted by ROS. In comparison to control cells, ROS levels were considerably lower following p-coumaric acid treatment. ROS stress is generally reported to be carcinogenic and to elevate metabolic activity. Since p-coumaric acid decreases ROS, it would therefore be a good exogenous potential to cause skin cancer cell death.